The National Academy of Medicine today announced that five members of the CUIMC facultySonia Yris Angell, Andrea Baccarelli, Wendy Chung, Kam W. Leong, and Patricia Stonehave been elected to the academy.

Members of NAM, formerly known as the Institute of Medicine, are elected by their peers in recognition of outstanding achievement. Membership is one of the highest honors bestowed in the field of medicine. The election reflects the high esteem of peers and colleagues. NAM members are part of a group of distinguished individuals who have made important contributions to health, medicine, and science.

Since 1970, when the Institute of Medicine was established as part of the congressionally chartered National Academy of Sciences, the organization's work and recommendations have shaped health research, practice, and policies that improve the lives of millions of people around the world.

The five new CUIMC members:

Sonia Yris Angell, MD, MPH, assistant clinical professor of medicine in theVagelos College of Physicians and Surgeons, was selected for her leadership in the nations first municipal regulation to ban transfat, launching national coalitions to reduce sodium and sugar in our food supply, working globally to improve control of hypertension, and for global leadership in modeling environmental change to sustainably reduce risk and save lives.

As a public health expert, Angell works on policies and programs that make places where we live, work, and play, healthier for all of us.She was previously deputy commissioner at New York City'sDepartment of Health and Mental Hygiene, overseeing the Division of Prevention and Primary Care, and was the founder and director of its Cardiovascular Disease Program. She also was a senior adviser for global noncommunicable diseases at the Centers for Disease Control and Prevention (CDC).

Andrea Baccarelli, MD, PhD, the Leon Hess Professor and Chair of the Department of Environmental Health Sciences in the Mailman School of Public Health, was selected for his pioneering work showing that environmental chemicals and lifestyle risk factors adversely affect the human epigenome, thereby producing adverse lifetime health consequences.

Baccarelli also serves as director of the Laboratory of Precision Environmental Health. An epigeneticist andclinical endocrinologist, Baccarelli helped develop powerful new tools in environmental epigenetics, not only to document the health risks of a variety of synthetic toxins, but also as an avenue to preventionand even targeted therapies. His lab has produced numerous publications at the intersection of epigenetics, molecular epidemiology, and environmental health.Over the course of his career, Baccarelli has expanded the vocabulary of epigenetics, showing how environmental damage inscribes itself in the body.

Wendy Chung, MD, PhD, the Kennedy Family Professor of Pediatrics and Medicine in theVagelos College of Physicians and Surgeons and leader of the Precision Medicine Resource in the Irving Institute, was selected for identifying the genetic basis for over 45 monogenic conditions (two of which bear her name) across a wide range of diseases and leading the pivotal study of newborn screening for spinal muscular atrophy.

Chung was the original plaintiff in the Supreme Court case that overturned the ability to patent genes and served on the Institute of Medicine's Committee on Genetic Testing. She is a board-certified clinical and molecular geneticist with 20 years of experience in human genetic research of monogenic and complex traits including diseases such as breast cancer, pancreatic cancer, congenital heart disease, pulmonary hypertension, inherited arrhythmias, cardiomyopathies, obesity, diabetes, congenital diaphragmatic hernias, and autism.

She has received the American Academy of Pediatrics Young Investigator Award, the Medical Achievement Award from Bonei Olam, the New York Academy Medal for Distinguished Contributions in Biomedical Science, and the Rare Impact Award from the National Organization of Rare Disorders. Chung is renowned for her teaching and mentoring and received Columbia University's highest teaching award, the Presidential Award for Outstanding Teaching.

Kam W. Leong, PhD, the Samuel Y. Sheng Professor ofBiomedical Engineering in the Fu Foundation School of Engineering and Applied Science (in Systems Biology in the Vagelos College of Physicians and Surgeons), was selected for his innovative developments in multifunctional nanoscale technologies for delivering drugs, antigens, proteins, siRNA, and DNA to cells.

Innovations in the Leong Lab focus on the design of therapeutic biomaterials for gene editing, drug and gene delivery, and regenerative medicine. He is developing nanocarriers that can deliver gene-editing elements to the liver for metabolic disorders, and studying the gene-editing efficiency in other tissues such as the brain and the gastrointestinal tract. Heis also working on the construction of human tissue-on-chips for disease modeling and drug development, particularly in using tissue-engineered blood vessel to model Marfan Syndrome and atherosclerosis, and generating patient-specific brain organoids to model neuropsychiatric disorders and opioid usage disorder.

Leong is internationally recognized as a leader in the development of nanoscale therapeutics. In 2013 he was elected to the National Academy of Engineering and theNational Academy of Inventors.

Patricia Stone, PhD, RN, the Centennial Professor of Health Policy and director of the Center for Health Policy in theSchool of Nursing, was selected for her expertise and sustained scholarly efforts in real-world comparative and economic evaluations of improving the quality of care and specifically preventing health care-associated infections.

Stone is dedicated to educating nurses in health policy methods as well as developing and disseminating knowledge that informs policymakers at the local, state, and national levels. She has a long history of research and has been the principal investigator on many federal and foundation-supported grants. She has served on a number of important policymaking committees, co-chaired two National Quality Forum Technical Advisory Panels, and served as an expert for the Massachusetts Expert Panel on Healthcare-Associated Infections and theCalifornia Health Department.

Her work on the cost of health care-associated infections hasbeen cited in major publications, Centers for Disease Control and Prevention guidelines, and the Health and Human Services Healthcare-Associated Infections Action Planand hascontributed to recent changes in health policy.

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Five Elected to the National Academy of Medicine - Columbia University Irving Medical Center

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After coming under investigation three times for quality control problems, consumer genetics company Orig3n last spring was allowed to administer COVID-19 tests in several states. By summer the Boston company halted testing in Massachusetts after producing hundreds of false positive test results.

Bailey the dog would likely be a skilled basketball player or boxer. Ginger the dog would probably experience mild trouble learning to read. And a few drops of kitchen sink tap water might need longer to develop skills required for language learning.

Those were a few of the findings of consumer genetics tests conducted by Boston-based startup Orig3n, a company that promises to tell customers how their DNA makeup could influence everything from cognitive abilities to sleep needs.

In all three cases, the company failed to identify the nonhuman samples sent to its labs by customers skeptical of Orig3ns products.

By the time the Massachusetts Department of Public Health received its second complaint in September 2018 about Orig3ns inability to identify canine DNA as nonhuman, a complaint that was also sent to the U.S. Food & Drug Administration, the company had already generated red flags at state and federal agencies tasked with ensuring labs that test human samples are operating properly starting in 2016, according to hundreds of pages of documents obtained by Gannett New England in a public records request.

Yet, in the spring, as COVID-19 spread across Massachusetts with fatal consequences especially among residents of long-term care facilities the FDA gave Orig3n an emergency authorization to perform coronavirus tests, and the DPH and the Centers for Medicare & Medicaid Services gave the company permission to add virology and immunology as specialties.

The DPH even recommended Orig3n as a testing option to nursing homes struggling to contain deadly coronavirus outbreaks across the state.

By August, however, the company had halted its COVID-19 testing operation when it was investigated once more, this time after DPH staff noticed Orig3ns lab was putting out an usually high number of positive coronavirus test results.

DPH investigators later found the company sent out at least 383 false positive COVID-19 test results to patients across the state between July 30 and Aug. 2. The false results put patients in immediate jeopardy, according to the DPH.

On Oct. 2, the Centers for Medicare & Medicaid Services sent a letter to Orig3n's lab director informing him the agency suspended the company's certificate to operate a clinical lab, and that it recommended a full revocation of that certificate. Orig3n has a right to appeal the decision within 60 days.

DPH investigators found serious deficiencies in the Boston-based labs coronavirus testing operation, some of which mirrored quality control issues found during previous investigations in 2018 and 2019.

But the pandemic offered an opportunity for Orig3n to fill a gaping need for increased COVID-19 testing capacity across the nation.

When COVID-19 became a public health crisis, Orig3n CEO Robin Smith wrote in an email to Gannett New England on Tuesday, we decided to dedicate our resources to providing testing for high-risk and high-need populations across the country, including school students and faculty, nursing home residents and staff, and private and public employers.

Smith did not answer a question about why the company was qualified to conduct coronavirus testing in light of its history of lab violations.

Investigations begin

Centers for Medicare & Medicaid Services, which enforces federal regulations for clinical labs testing human samples, first investigated Orig3ns Massachusetts lab on Jan. 31, 2018.

While documents dont say what prompted the investigation, they show a federal surveyor found a litany of deficiencies at Orig3ns Waltham lab, which the company had recently acquired.

The surveyor found the lab didnt have a system in place to ensure test results and other patient-specific information were accurately and reliably sent to their final destinations. The lab also failed to show that a legally authorized person made requests for the genetic tests processed by Orig3n.

Four months later, shortly after the company told federal regulators it had corrected deficiencies outlined in the January investigation, the Massachusetts DPH sent its own surveyor to inspect the companys lab operation, according to DPH documents.

The DPHs May 2018 investigation was sparked by a May 2, 2018, report by NBC 5 in Chicago. The news organization sent dog DNA to similar at-home genetic testing companies and found that Orig3n was the only company not to flag the dog sample as unreadable.

The DPH surveyor ultimately concluded that Orig3n had corrected issues with its testing process when it underwent the Clinical Laboratory Improvement Amendments (CLIA) certification established by the Centers for Disease Control and Prevention, which occurred after NBC 5 sent the dog DNA for processing. The surveyor concluded no further action was required.

Quality control lacking

In 2019, Centers for Medicare & Medicaid Services sent out another surveyor for the third investigation of Orig3n by lab regulators in two years.

The surveyors visit came shortly after Bloomberg published an article in which 17 former Orig3n employees alleged the companys consumer genetic testing kits which ranged in price from $29 to $298 sometimes failed to work as advertised and were often contaminated or inaccurate.

The surveyor found a long list of quality control issues at the lab, which had by then moved from Waltham to Bostons Seaport after scoring millions of dollars in venture capital from backers. One of those backers, LabCorp, operates one of the largest clinical lab networks in the world.

Echoing findings by previous investigators, basic records were inaccessible or missing, including reports that showed equipment and instruments were properly maintained and tested according to manufacturer guidelines. The surveyor also found the lab had failed to ensure that the temperature of refrigerators and freezers that contained patient samples and reagents were monitored and logged, a key protocol for making sure testing functions correctly.

Roughly four months after Orig3ns lab director told regulators the company had corrected or would correct the issues identified in the 2019 investigation, the FDA sent a letter notifying the company it was approved for inclusion under an umbrella Emergency Use Authorization to conduct certain types of COVID-19 testing.

In a press release announcing the news, Orig3n said the company's coronavirus testing would be available to authorized health care providers and institutions nationwide.

FDA spokesperson Jim McKinney told Gannett New England on Tuesday the agency authorizes tests, not labs.

Qualifying a lab as CLIA certified would be a function of the Centers for Medicare & Medicaid Services, McKinney wrote in an email.

A Centers for Medicare & Medicaid Services spokesperson told Gannett New England on Wednesday that the FDA has sole authority to issue emergency authorizations, but as a CLIA-certified lab, Orig3n was authorized to conduct high-complexity testing.

The spokesperson also said the agency affords labs due process and an opportunity to address allegations of noncompliance. When Orig3n began COVID-19 testing, the spokesperson said, the Massachusetts DPH had deemed the lab fully compliant.

In May, both the Massachusetts DPH and Centers for Medicare & Medicaid Services concluded after offsite surveys that the company could add virology and immunology as specialties. The agencies found the company was in full compliance with applicable state licensure and CLIA requirements.

In statements to Gannett New England, spokespeople for both Centers for Medicare & Medicaid Services and the DPH said offsite approvals for the addition of specialties to CLIA-certified labs are standard procedure. Usually the surveys involve a desk review of documentation including procedures, personnel qualifications and training.

With approvals in place, Orig3n began conducting coronavirus testing across Massachusetts, and offering its COVID-19 testing services in other states.

In a memo to nursing homes last updated on June 1, the DPH recommended the companys testing services to long-term care facilities sprinting to meet a May 25 deadline to test 90% of residents and staff for the virus. The company would eventually conduct coronavirus testing for at least 60 nursing homes statewide, most of which were dealing with deadly outbreaks.

Test results prompt fourth investigation

Records show federal regulators visited Orig3n twice in August 2020 after the company reported an unusually high number of positive COVID-19 test results. Earlier in the month, the company voluntarily agreed to halt COVID-19 testing.

On Aug. 8, Sandra Smole, director of the Massachusetts State Public Health Laboratory, sent an email to public health leaders in other states alerting them about Orig3ns high rate of positive COVID-19 tests. Smole classified the email's importance as "high" and sent it to public health officials in California, Michigan, Ohio and North Carolina, as well as the Association of Public Health Laboratories.

"The Orig3n Inc. Laboratory Director indicated that they also test specimens from your jurisdiction, and so we wanted to make you aware of this situation," Smole wrote. "At this time, we have no specific information indicating that samples from your state have been impacted."

DPH documents did not indicate if there were problems with Orig3n COVID-19 test results in other states.

On Aug. 26, the Massachusetts DPH Division of Health Care Facility Licensure and Certification finished its investigation into Orig3ns coronavirus testing operation, which found dangerous deficiencies in how the lab conducted its work.

According to the report, the lab failed to document basic sanitation measures, including the daily sanitizing of lab benches and equipment used in COVID-19 testing. The labs system for detecting potential errors in test results was inadequate, and lacked controls that would detect contamination.

Both Orig3ns lab director and its CEO confirmed in interviews with investigators that, while the lab tracked daily positivity rates, it failed to assess or correct any problems flagged by higher than normal positivity rates.

The report also slammed Orig3ns lab director for failing to provide overall management and direction, which meant the director was unable to ensure the accuracy and reliability of patient test results.

Orig3n began coronavirus testing on April 27. Before it suspended COVID-19 testing in early August at the states request, the company had reported 23,513 results.

The Massachusetts DPH ultimately found the company sent out at least 383 false positive results to patients, according to agency documents, but because not all test samples processed by Orig3n were retested, that number could be higher.

Its also unknown how many false negative coronavirus test results the company released to people, because false negative test results are harder to detect than false positives.

The DPH told Orig3ns lab director in a Sept. 4 letter that the companys deficiencies posed immediate jeopardy to patient health and safety, meaning the lab caused, was causing, or was likely to cause serious injury or harm, or death, to individuals served by the laboratory or to the health and safety of the general public.

Orig3n has not yet restarted coronavirus testing, according to Orig3ns CEO. The company is waiting for resolution of our regulatory discussions with CMS (Centers for Medicare & Medicaid Services) and the state of (Massachusetts), Smith said in a statement to Gannett New England.

In an interview for a previous story by Gannett New England about the DPHs investigation into Orig3ns coronavirus testing, Dr. Michael Mina, an assistant professor of epidemiology at Harvard T. H. Chan School of Public Health who has experience running laboratories, said mistakes do happen at labs, but they don't usually require an investigation.

It's just important to keep all these things in check, Mina said in September. The frenzy to do coronavirus testing has been so extreme. I don't think labs should be immediately shut down for mistakes, but we have to remain vigilant to ensure that all the testing that is being done is up to the highest standards.

Jeannette Hinkle and Trevor Ballantyne are reporters for Gannett New England.

Dive deeper into the companys history in this timeline:

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Orig3n analysis IDd dog and tap water DNA as human. Then the company produced hundreds of false positive COVID-19 test results. - The Gardner News

Recommendation and review posted by Bethany Smith

Had these survivors never been genetically tested they would not have known why they had suffered a near-fatal arrest or that their families were also at risk, senior author, and director of RPAs Genetic Heart Disease Clinic Professor Chris Semsarian said.

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"These are young people some in their teens and 20s who on a particular day had a cardiac arrest and for so long we didnt know what the reason was," he said.

"You can do every test under the sun and you dont find anything wrong with their heart. It looks normal, but it carries genetic mistakes."

Without genetic testing, any medical team may come to the conclusion a cardiac arrest was likely to be a freak event, requiring no ongoing treatment, leaving patients vulnerable to a possibly fatal second attack.

The genetic testing was detecting "concealed cardiomyopathies", and could be used as an early-warning system that the hearts electrical system was short-circuiting.

The study authors suspect patients such as James Medway will develop outward signs of cardiomyopathy years later, such as an enlarged or thickening of the heart.

"This is precision medicine in action using genetics to pinpoint the precise cause of the disease, screen their families and find targeted treatments that may be as simple as lifestyle changes or medication or it may be an implanted defibrillator, but its all geared towards preventing sudden death in the future," Dr Semsarian said.

Mr Medway was in peak physical condition "fantastically fit", the Olympic rowing hopeful says as he trained at the Australian Institute of Sports training centre in northern Italy in 2019.

Then he blacked out.

When he was roused from an induced coma two days later, his teammates had to fill him in.

The 27-year-old had finished his warm-down after intense training. Just as he unstrapped his feet from a rowing machine he collapsed, hitting his head on the ergometer.

"It was such a pivotal, live-or-die moment," Mr Medway said.

James Medway, now 28 years old, in Hyde Park, Sydney. Credit:Louise Kennerley

The rower knew he was lucky. Had he been training on the lake, had one of his teammates a doctor not immediately suspected his heart and not his head injury was the critical concern, and the medical team not been nearby with a defibrillator, he could have died.

But after exhaustive testing, his heart looked normal for an elite athlete slightly on the larger side, and healthy. Within a week, he was fitted with an implantable cardioverter-defibrillator and less than two months later he was back training.

"There was a chance this was just a freak accident and I definitely still had the dream of getting to the Olympics and winning a medal," he said.

But Professor Semsarian, one of Mr Medways doctors, knew there was a small chance the episode had a genetic cause. Testing confirmed it.

Mr Medway had arrhythmogenic cardiomyopathy linked to a genetic mutation, which is estimated to affect one in 5000 people, most of whom never have a cardiac episode.

But elite-level sport was out of the question.

"It was a lot to take in," Mr Medway said. "I prided myself on being a really fit and healthy person, and the fact that I never got sick or injured. Now something I excelled at was no longer good for me.

Roughly 33,000 Australians have a sudden cardiac arrest every year; 9 per cent survive. The vast majority of cases are people over 35 with coronary heart disease and well-established risk factors like smoking and high blood pressure.

Younger patients with these unexplained cardiomyopathies are uncommon, and most can avoid having one of these near-death experiences. But for those who do, the ramifications can be tragic.

"Looking back, it would be very easy to slip into the mentality where everything I was working towards has been taken away but Im so lucky to have had that experience," said Mr Medway, who has launched into a career he loves as an investment banking analyst.

The scientists have so far genetically tested 11 first-degree relatives of survivors. Five had the same inherited genetic mutations and six were given the relieving news that they did not, the International Journal of Cardiology reported.

Dr Isbister said genetic testing could provide the answers when all other causes have been excluded, but guidelines written about a decade ago dont support this approach.

"What we have seen here is that there is perhaps more utility for patients with no clinically identified causes to have genetic testing now that our knowledge of cardiac arrest and genetics has advanced and we can cast a wide [genetic testing] net to get answers for patients," she said.

The authors suggested all sudden cardiac arrest survivors under the age of 50 could have an assessment to determine whether genetic testing was warranted.

Professor Jason Kovacic, executive director of the Victor Chang Cardiac Research Institute, said the research showed the benefits of comprehensive genetic testing.

"It does indicate that we can potentially save lives here," he said.

But the single-centre study of 36 patients was not likely to be enough to alter diagnostic practice, he said.

"Its a challenge to recruit thousands of patients because while always a tragedy this is relatively uncommon in our community," Professor Kovacic said.

"Whether this will tip the scale to make [cardiology] committees change their guidelines is yet to be determined."

Kate Aubusson is Health Editor of The Sydney Morning Herald.

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Hidden cause of cardiac arrests uncovered in perfectly healthy hearts - Sydney Morning Herald

Recommendation and review posted by Bethany Smith

Trusted Business Insights answers what are the scenarios for growth and recovery and whether there will be any lasting structural impact from the unfolding crisis for the Hereditary Testing market.

Trusted Business Insights presents an updated and Latest Study on Hereditary Testing Market. The report contains market predictions related to market size, revenue, production, CAGR, Consumption, gross margin, price, and other substantial factors. While emphasizing the key driving and restraining forces for this market, the report also offers a complete study of the future trends and developments of the market.The report further elaborates on the micro and macroeconomic aspects including the socio-political landscape that is anticipated to shape the demand of the Hereditary Testing market during the forecast period.It also examines the role of the leading market players involved in the industry including their corporate overview, financial summary, and SWOT analysis.

Get Sample Copy of this Report @ Hereditary Testing Market Size, Market Research and Industry Forecast Report, 2020-2026 (Includes Business Impact of COVID-19)

Industry Insights, Market Size, CAGR, High-Level Analysis: Hereditary Testing Market

The global hereditary testing market size was valued at USD 5.8 billion in 2019 and is projected to register at a CAGR of 6.3% during the forecast period. The expanding reproductive genetic health space is one of the key market drivers. Key players, such as Natera, have reported a continuous increase in test volumes in womens health genetic testing for inherited conditions. This reflects the growing acceptance of hereditary tests among the population, thereby accelerating the revenue growth.Furthermore, a consistent rise in demand for newborn screening has led to an increase in sales of DNA testing kits. For instance, in November 2019, the Division of Consolidated Laboratory Services (DCLS) of the Virginia Department of General Services screened 7,868 newborns for nearly 31 hereditary and metabolic disorders. Increasing penetration of newborn screening across the globe is further aiding in the revenue growth.

Reforms in genetic testing guidelines have led to inclusion of multigene panel testing for hereditary cancer into clinical practice. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for breast, ovarian, and colorectal cancers offers information on some of the cancer risk factors and management recommendations for single and multiple gene panels.Gradual developments in the distribution model is likely to benefit the genetic testing market. Technology providers are playing a crucial role in the market growth by improving their distribution service and increasing the efficiency of technology. Companies are using a cloud-based distribution model to make bioinformatics technology available for use by other laboratories. As of March, 2019, around 14 licensees were using Constellation software commercially for the marketing of Non-invasive Prenatal Testing (NIPT) products.Although these hereditary tests have huge advantages over conventional tests, several industry experts cited the cost and security concerns faced by consumers pertaining to the test. Moreover, lack of effective regulation of the tests is another key area that demands focused efforts. Despite these challenges, the genetic testing market is constantly expanding owing to the advantages of these innovative tests along with improved healthcare outcomes.DiseaseType Insights of Hereditary Testing Market

Product and service offerings with regard to various hereditary cancer testing continue to expand. Entry of major players, such as Quest, in this segment in the recent past, has significantly driven the hereditary testing market. Considering breast cancer genetic testing as a lucrative source of revenue, companies are focusing on business strategies to enhance their presence in this segment.One of the strategies is offering hereditary tests at a price lower than that offered by competitors. For instance, Color Genomics began selling its product for USD 259, whereas similar products offered by Myriad cost around USD 4,000. The increasing affordability of the tests is one of the key drivers of this segment. Furthermore, BRCA1 carriers have an 80% risk of developing breast cancer, which has also accelerated the developments in hereditary cancer testing market.

On the other hand, lung cancer is one of the major cancer forms that has a relatively few number of products. This is because most cases of lung cancer are not related to inherited genetic mutations. Similarly, for cervical cancer, most of the cases are caused by Human Papilloma Virus (HPV) and not genetic mutations. Lack of effective evidence over heritability of cervical cancer are driving the research activities in this market.Prenatal testing, irrespective of the associated risks, is increasingly gaining popularity. The cell-free DNA (cfDNA)-based NIPT testing is considered medically necessary by Anthem Blue Cross and Blue Shield of California. Previously, these players promoted cfDNA-based NIPT testing for trisomys 21, 18, and 13 only in high-risk pregnancies, as determined by maternal age and other factors.

Regional Insights of Hereditary Testing Market

Variations in regulatory frameworks pertaining to genetic tests across the world have significantly impacted the approval and commercialization of tests in the global market. Currently, a wide variety of genetic tests are being provided by several key companies in U.S. as well as several countries in Europe, Asia Pacific, and other regions.Europe accounted for the largest share in terms of revenue in 2019 and is likely to continue its dominance during the forecast period. This can be attributed to presence of key players providing genetic tests, high adoption of advanced treatments, and recommendations provided by government agencies to ensure the quality of hereditary testing services.In September 2019, Blueprint Genetics, a Finnish company, partnered with ARCHIMEDlife, a rare disease diagnostics company, to provide biochemical testing for rare diseases in North America. Through this partnership, both firms planned to diversify their range of genetic disease testing services to serve the customers better. Such initiatives are expected to strengthen the genetic testing scenario for hereditary disorders in North America, thereby accelerating regional revenue generation.

Market Share Insights of Hereditary Testing Market

Understanding the role of genetic mutation in disease occurrence has significantly accelerated the R&D in this market. Various retrospective studies are being carried out to understand the role of inherited mutations in disease pathology, which has led to key diagnostic developers, such as Quest Diagnostics, enter the market. Continuous authorizations and approvals of genetic tests by the government is expected to propel the organic revenue growth of operating companies.Some of the key players engaged in offering services and products in this market are Myriad Genetics, Inc.; Invitae Corporation; Illumina, Inc.; Natera, Inc.; Laboratory Corporation of America Holdings; F. Hoffmann-La Roche Ltd; Quest Diagnostics Incorporated; CooperSurgical, Inc.; Agilent Technologies, Inc.; Thermo Fisher Scientific, Inc.; Twist Bioscience; Sophia Genetics; Fulgent Genetic, Inc.; Medgenome; and CENTOGENE N.V.Furthermore, the expanding product portfolio is indicative of growing competition in the market. Each company is making focused efforts to offer products with competitive advantage. For example, cross-selling efforts by Natera helped the company witness lucrative revenue generation over the past years. The company promotes collective use of Horizon and Panorama products for women who have not undergone carrier screening tests in their first trimester.

Segmentations, Sub Segmentations, CAGR, & High-Level Analysis overview of Hereditary Testing Market Research ReportThis report forecasts revenue growth at global, regional, and country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2015 to 2026. For the purpose of this study, this market research report has segmented the global hereditary testing market report on the basis of disease type and region:

Disease Type Outlook (Revenue, USD Million, 2019 2030)

Hereditary Cancer Testing

Lung Cancer

Breast Cancer

Colorectal Cancer

Cervical Cancer

Ovarian Cancer

Prostate Cancer

Stomach/Gastric Cancer

Melanoma

Sarcoma

Uterine Cancer

Pancreatic Cancer

Others

Hereditary Non-cancer Testing

Genetic Tests

Cardiac Diseases

Rare Diseases

Other Diseases

Newborn Genetic Screening

Preimplantation Genetic Diagnosis & Screening

Non-invasive Prenatal Testing (NIPT) & Carrier Screening Tests

Looking for more? Check out our repository for all available reports on Hereditary Testing in related sectors.

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Hereditary Testing Market Size, Market Research and Industry Forecast Report, 2020-2026 (Includes Business Impact of COVID-19) - Eurowire

Recommendation and review posted by Bethany Smith

It is time for genetics services to rethink where they are focusing their resources, argue two genetic counsellors with experience of working in NHS specialist genetic services, research, and policy

Genomic testing is increasingly a part of mainstream healthcare and is positioned high on the political agenda (Chief Medical Officers Report 2017,EU Commission). A recent UK government report (Genome UK) and previous announcements by Matt Hancock, the Secretary of State for Health and Social Care, have raised the profile of genomics as a technology offering significant benefits to patients in terms of predicting and diagnosing disease, as well as personalising treatments. Initiatives such as the 100,000 Genomes Project, changes in the delivery of laboratory genetic services in the NHS in England, and the launch of the new NHS Genomic Medicine Service, mean that genomic technology is here to stay.

Commentators have raised concerns about the benefits of such testing in healthy individuals, and the problems for clinical services left to pick up the pieces by consumers who have accessed genetic testing directly (RCGP 2019). These issues are entirely relevant, and authors rightly argue for caution in widespread implementation of genomic technologies where they may not be clinically relevant. Legal cases have also highlighted ethical tensions between who has a right to know or withhold genetic information (Middleton A et al 2019).

We want to change the focus and raise some issues around the care of patients with rare genetic diseases and their families.

Access to clinically relevant genomic testing for these families is easier than it has ever been before. It means there will be a reduction in the diagnostic odyssey, shortening the time between initial suspicion of a genetic disorder to confirmed diagnosis. New disease mechanisms and classifications will emerge. More patients will have an explanation as to the cause of their own condition and any familial implications. More parents will have an explanation of their childs condition and the possible chances of it happening again in future children.

Access to genomic testing is pivotal for families with rare diseases, but the focus of clinical care should move beyond just access to the test itself to include the post-test consequences. By this we mean offering support for patients coming to terms with diagnosis of a rare genetic disorder and managing the information the genetic result gives in relation to immediate care and potential choices, as well as the care of family members and future generations. The current pandemic has also had a significant impact on families living with rare disease. (Genetic Alliance. Family story: thoughts on Covid-19).

In the short to medium term the contribution genomics makes to medicine will mostly happen within the field of rare genetic diseases. As stated in many policy documents, rare diseases may be individually rare, but as a group they affect 1 in 17 of us, which means genomic testing is relevant to a significant proportion of patients using health services.

As diagnostic genomic testing increases, all these patients and their families will need healthcare directed at mediating the consequences of diagnoses that are made or recognised. In a global healthcare service with limited availability of genetic health professionals (Abacan 2019) it is time to push existing resources to where they are needed most.

We already know from various reports that families with rare diseases face many difficulties in managing their complex care (EURORDIS,All Party Parliamentary Group (APPG) on Rare, Genetic and Undiagnosed Conditions). We also know from anecdotal experience and research that the following are very relevantthe lifelong nature of genetic disorders, the fact that they may affect many different body systems requiring holistic coordination of care, and the fact that they may have intergenerational consequences and risks. All present challenges for the way health systems are currently constructed and care is delivered.

Traditionally, genetic services and genetic counselling have been focused on the test. This has been enshrined in various international guidelines and instruments, with some countries mandating genetic counselling before people are able to access a genetic test (Kalokairinou et al 2017). As the availability of genomic testing increases, it is time to question where genetic services could be focusing their resources.

Decisions around proceeding with a genomic test in pre-test counselling include many facets that are well-rehearsed in clinical practice. For example, who is chosen for testing, who has access to the test result, consent choices, and the challenges of interpreting and communicating the results. Once clinically relevant genetic analysis is a routine part of diagnostic pathways in mainstream medicine, the focus of genetic counselling needs to shift from the pre-test phase to post-test care. This requires genetic services and genetic health professionals to question custom and practice, to consider what is necessary and useful and what is no longer fit for purpose.

This will require a shift in thinking within the clinical genetics community. We are letting patients and families down if we do not put as much emphasis on their care after genomics analysis as we currently put on it before. Constrained NHS resources means we must be flexible, consider how to do things differently and let go of past practices and service models to explore new ways of working.

Christine Patch has 40 years experience as a nurse and registered genetic counsellor. She is principal staff scientist for genomic counselling at the Society and Ethics Research Group, Wellcome Genome Campus, Connecting Science, Cambridge, and lead genetic counsellor for Genomics England.

Anna Middleton has 26 years experience as a registered genetic counsellor and social science researcher. She is head of society and ethics research at Wellcome Genome Campus, Connecting Science, Cambridge, and has personal experience as a patient in the 100,000 genomes project.

Competing interests: None declared.

This work was supported by Wellcome grant [206194] paid to Society and Ethics Research Group via Connecting Science, Wellcome Genome Campus. AM receives personal fees as a member of the Ethics Board for the patient company RareMark. CP is employed by Genomics England a company wholly owned by the Department of Health & Social Care.

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As genomic testing increases, it is time to focus on post test care for patients - The BMJ - The BMJ

Recommendation and review posted by Bethany Smith

The Global DirectToConsumer (DTC) Genetic Testing Market is broadly and deeply studied in the report with a key focus on the competitive landscape, regional growth, market segmentation, and market dynamics. We have used the latest primary and secondary research techniques for compiling this comprehensive research study. The report offers Porters Five Forces analysis, PESTLE analysis, competitive analysis, manufacturing cost analysis, revenue and production analysis, and various other types of analysis to provide a complete view of the global DirectToConsumer (DTC) Genetic Testing Market. Each segment of the global DirectToConsumer (DTC) Genetic Testing market is carefully analyzed on the basis of market share, CAGR, and other vital factors. The global DirectToConsumer (DTC) Genetic Testing market is also statistically presented with the help of Y-o-Y growth, CAGR, revenue, production, and other important calculations. The report presents the market competitive landscape and consistent in-depth analysis of the major vendor/key players in the market along with the impact of economic slowdown due to COVID.

Global DirectToConsumer (DTC) Genetic Testing market competition by top manufacturers, with production, price, revenue (value) and market share for each manufacturer;

the top players including

Get PDF of DirectToConsumer (DTC) Genetic Testing Market report template: https://www.amplemarketreports.com/sample-request/covid-19-outbreak-global-direct-to-consumer-genetic-testing-industry-2074209.html

On the basis of product, this report displays the production, revenue, price, market share, and growth rate of each type, primarily split into

On the basis of the end users/applications, this report focuses on the status and outlook for major applications/end users, consumption (sales), market share and growth rate for each application, including

Key questions answered in the DirectToConsumer (DTC) Genetic Testing Market report by the research study:

What impact does COVID-19 have made on DirectToConsumer (DTC) Genetic Testing Market Growth & Sizing?

What will be the behavior of market participants?

What strategies will market players adopt to sustain their growth?

Which segment will lead the market?

Which region will offer the most number of opportunities?

What are the key drivers, restraints, and trends of the market?

What will be the market size between 2019 and 2025?

Our report includes ongoing and latest market trends, company market shares, market forecasts, competitive bench-marking, competitive mapping, and in-depth analysis of key sustainability tactics and their impact on market growth and competition. In order to estimate the quantitative aspects and segment the global DirectToConsumer (DTC) Genetic Testing market, we used a recommended combination of top-down and bottom-up approaches. We studied the global DirectToConsumer (DTC) Genetic Testing market from three key perspectives through data triangulation. Our iterative and comprehensive research methodology helps us to provide the most accurate market forecasts and estimates with no to minimum errors.

Industry Matrix Analysis of DirectToConsumer (DTC) Genetic Testing Market:

As part of our quantitative analysis, we have provided regional market forecast by type and application, market revenue forecasts and estimations by type, application, and region up to 2025, and global DirectToConsumer (DTC) Genetic Testing market revenue and production forecasts and estimations up to 2025. For qualitative analysis, we have concentrated on policy and regulatory scenarios, component benchmarking, technology landscape, key market issues, and industry landscape and trends.

We have also focused on technological edge, profitability, business size, company strengthens in relation to the industry, and analysis of products and applications in terms of market growth and market share.

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Table of Contents:

Report Overview: It covers the scope of the research study, companies profiled in the report, objectives of and years considered for the research study, and highlights of type, application, and regional segmentation. As part of the highlights of segmental analysis, this section discloses growth rates and market shares of segments.

Executive Summary: It includes analysis of the global market size, the market size by region, and industry trends. Under market size by region, this section concentrates on growth rates and DirectToConsumer (DTC) Genetic Testing market shares. Under industry trends, it focuses on market use cases and top trends of the market.

Key Players: Here, revenue by manufacturer, funding and investment analysis by player, expansion plans, mergers and acquisitions, and company establishment dates are included.

Geographical DirectToConsumer (DTC) Genetic Testing Market Analysis: This part of the report assesses key regional and country-level markets on the basis of market size by type and application, key players, and market forecast.

Profiles of International Players: All of the companies profiled in this section are deeply evaluated, keeping in view their prices, gross margin, revenue, sales, and core and other businesses. This section also gives company details, a business overview of players, and other information.

DirectToConsumer (DTC) Genetic Testing Market Dynamics: Here, the report provides supply chain analysis, regional marketing analysis by type and application, and analysis of market drivers, restraints, and opportunities.

Appendix: It includes author details, a disclaimer, data sources, research approach, and research methodology.

Breakdown by Type, Application, and Region

Key Findings of the Report

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Stay Tuned with the Epic Battle in the DirectToConsumer Genetic Testing Market - TechnoWeekly

Recommendation and review posted by Bethany Smith

Moles have a pretty tough life. They live underground, in the dark, burrowing through heavy dirt. And when faced with an enemy, there's nowhere to turn they have to fight.

In most mammals, females tend to be at a disadvantage when it comes to face-to-face combat, because they tend to be smallerand less aggressive than males.

But female moles have evolved a secret weapon: a hybrid organ made up of both ovarian and testicular tissue. This effectively makes them intersex, giving them an extra dose of testosterone to make them just as muscular and aggressive as male moles.

"As a consequence, basically the whole body of the female, they get masculinized," geneticist Daro Lupiez told Quirks & Quarks host Bob McDonald. "They become the body builders of nature."

Lupiez co-led a study to understand how the moles' genes facilitated this advantage, which was recently published in the journal Science.The research was part of a collaboration between the Max Planck Institute for Molecular Genetics and the Max Delbrck Center for Molecular Medicine in the Helmholtz Association in Germany.

The team worked with Iberian moles, commonly found in Spain and Portugal, however this intersex adaptation has been documented in at least six mole species.

"We know that intersexuality happens in species like humans, dogs or cats. But the difference actually in moles, it happens all the time, so all the females are intersexual. And this is really something unique among mammals,"said Lupiez.

To understand why this happens, the researchers completely sequenced the genome of the Iberian mole and sifted through their billions of genetic "letters" or nucleotides, looking for thoseresponsible for the change.They also comparedthe mole genometo several other animals, including humans. "I can really tell you that this is like looking for a needle in a haystack," said Lupiez.

They found that it wasn't the genes that had changed, but ratherthe regulatory elements, or instructions, associated with those genes, which gave the female moles this advantage.

"In moles, you have all the components there, but the only thing is that there have been new connections established," he said. "These new genes get completely different patterns of expression, and they start to make new functions which in this case is to help females develop as intersexual."

As a result of these different genetic instructions, the moles develop an organ made up of both ovarian and testicular tissue. This organ, called ovotestis, still functions as an ovary, but doesn't produce sperm. It does, however produce the same large amounts of testosterone as found in male moles.

This hormonal boost means that females and males are roughly the same size, equally muscular, and equally aggressive. Even their external genitalia looks alike, with the female's clitoris protruding much like the male's penis.

This boost of testosterone doesn't affect the molesfertility or reproductive abilities.

"What normally happens within mammals is that the males have these famous Y chromosomes and females do not. So this is exactly the same for moles," Lupiezsaid. "So from this perspective, you have two completely separate sexes."

He adds that this natural doping can make it very challenging for researchers in the fieldto figure out whether a mole is a male or a female.

"It took me quite a while of trying to really figure out when I had a female in front of me or a male," he said. "They are pretty tough ... they become pretty aggressive and pretty wild to handle. But you know, with time we learn how to handle them with care."

Produced and written by Amanda Buckiewicz.

Here is the original post:
Female moles are intersex they have testicle-like tissue that helps them grow big and tough - CBC.ca

Recommendation and review posted by Bethany Smith

Humans come in all shapes and sizes, as well as in varying heights. These factors are primarily dictated by your genes. If you have taller-than-average parents, chances are youll be tall, too.

Your genes can also determine when youll experience growth spurts, which can sometimes make some people much taller than their peers at the same age.

Theres nothing inherently wrong with being tall. Many of the concerns with being taller than others derive from negative and very much outdated stereotypes.

In rare cases, there may be underlying medical issues that make some children grow taller than usual at a noticeably young age. Unless you have a medical concern, you should never try to stop yourself from growing taller.

Keep reading to learn more about how we grow and what determines how tall well be.

In short, there isnt a way you can limit how tall youll be unless theres an underlying medical issue at hand.

Concerns over being too tall primarily stemmed from psychosocial considerations that were prominent between the 1950s and 1990s.

In the United States, such concerns were often aimed at adolescent girls whose parents were concerned their daughters might become too tall and possibly not get married.

Such fears stemmed from the sexist idea that women werent supposed to be taller than men. These concerns were significant enough that some families opted for hormone treatments for their daughters via estrogen.

It was thought that estrogen therapy could help stop girls from growing taller. However, research shows that not only was estrogen not proven effective in preventing a tall stature, but many women also reported unpleasant side effects.

While attitudes surrounding marriage and the ideal partner have certainly evolved, there may be other areas of concern surrounding height that are medically relevant.

These include medical conditions that cause children to grow tall too quickly, such as Marfan syndrome and pituitary gland tumors.

Unless you have a legitimate medical concern, you should not try to stop growing taller.

On the flipside, some people are concerned that they might be shorter than average. These may be caused by medical conditions and are usually detected during childhood. Some of the causes include:

Treatment for a shorter than average stature depends on the underlying cause, and it must be evaluated before adulthood.

Human growth hormones may help increase height in children who have hormone deficiencies. Surgery may also be helpful in cases of achondroplasia.

Your genes are the primary factors that govern how tall youll be.

Such genetics can vary based on region and ethnicity, too. Chances are, if your parents are taller or shorter than average, then youll end up being around the same height.

However, there are also some gray areas to consider. For example, if you have one tall and one short parent, your own height may end up being somewhere in between.

Its also not out of the realm of possibilities to be an anomaly in your family, where you may be significantly taller or shorter than everyone else.

Childhood nutrition and overall health play other factors in determining your height. Developed countries have witnessed increasing heights in their populations thanks to better access to food and health care.

On the flipside, poor nutrition, inadequate health care, and premature birth can all contribute to a shorter than average stature.

As you age, hormones become crucial drivers of growth. Human growth hormones produced in the pituitary gland are the most influential, followed by sex hormones (estrogen, testosterone) and thyroid hormones.

A final consideration is your gender. Girls sometimes grow quicker than boys at the same age due to hitting puberty about 2 years earlier. However, boys tend to have larger growth spurts overall. This results in adult men being about 5 inches taller than adult women.

You should talk to a doctor if you have any concerns about your height. They can rule out the possibility of any underlying medical conditions. Theyll also likely offer reassurance about being taller.

Its also important to see your doctor for a physical every single year. If youre a parent, a pediatrician can determine where your child falls on a growth chart compared to other children their age.

Some children grow quicker (and end up being taller) than their peers, but this doesnt usually indicate a medical problem. Your doctor will let you know if your individual height and growth rate indicates any concerns.

Despite some social and cultural perceptions on height, theres nothing inherently wrong with being tall. To gauge how tall youll be, look to your parents own heights as a guide.

In rare cases, a medical condition might make you extremely taller than whats considered normal. Your doctor can help determine whether your taller-than-average height is of any concern.

Unless youre being treated for a medical condition that contributes to your tall stature, there isnt any treatment that stops you from achieving your full height. If concerns persist, talk to your doctor for advice.

Visit link:
How to Stop Growing Taller and Why You Shouldn't - Healthline

Recommendation and review posted by Bethany Smith

by Matthew RosenbergDALTON: Sitting in the local Republican office most days is a lifelong conservative named Diane Putnam, who got her first taste of politics when Dwight D. Eisenhower was president and she was a little girl telling people that she liked Ike.

She still does. But these days, what really grabs Putnams attention is talk of a satanic criminal conspiracy hatched by a cabal of deep state child molesters who are seeking to take down President Donald Trump. In other words, she believes in QAnon. She insists she is just one of many.

The large majority of people, they understand about QAnon, Putnam, the Republican chairwoman of this small Georgia city, said in a recent interview.

Those that dont know, she added, they have not looked into really what its about.

Across the country, Republicans like Putnam long-standing party members who could hardly be described as fringe radicals are embracing QAnon. The followers of this online phenomenon believe that the Democratic establishment and much of the Republican elite are deeply corrupt, and that Trump was delivered to save America from both. Urged on by the president, whose espousal of conspiracy theories has only intensified in the waning weeks of his campaign, QAnon adherents are pushing such ideas into the conservative mainstream alongside more traditional issues like low taxes and limited government.

There was no acknowledgment of the real-world violence inspired by QAnon, which has prompted a preelection crackdown by social media networks, with YouTube last week becoming the latest platform to attempt to stop its spread. But dozens of recent interviews in Georgia and other parts of the country offered insights into the pull of a movement that has migrated far beyond the confines of the internet and, much like the Tea Party before it, plays to the sense of grievance on which Trumps political career was built.

People feel left out, said McKray Kyer, 24, the local Republicans vice chairman. QAnon, with its focus on criminal elites, helped them understand why. Its not about what were doing wrong its the swamp.

Kyer said he had looked into QAnon and was not sure what he believed. But many others interviewed said they believed in some or most of QAnon, and a significant portion of those who did not know the movements name were familiar with its themes, especially its talk of rampant child trafficking and devil worship among powerful elites.

Yet the movement is elastic, drawing on any number of well-worn tropes. Even people who explicitly dismissed QAnon as lunacy often volunteered similar conspiracy theories. There was talk of how the pandemic was an outright hoax or, at the very least, being wildly overblown. Many people repeated racist theories about former President Barack Obama or the anti-Semitic notion that financier George Soros controls the political system.

Its a real undercurrent in the party, said Jason Anavitarte, 42, a Republican running for the Georgia State Senate. Its QAnon; its other conspiracy theories. We hear them every day.

Or as Michael Conley, 42, a Trump supporter and QAnon adherent from Hagerstown, Maryland, put it: Everybodys talking about it.

Though there has been little public polling, there is growing anecdotal evidence that QAnon followers now make up a small but significant minority of Republicans. Adherents are running for Congress and flexing their political muscles at the state and local levels. The movements growth has picked up pace since the onset of the pandemic in March, and its potency is clear on social media before Facebook banned QAnon content earlier this month, there were thousands of dedicated Facebook groups with millions of members.

The phenomenon can be seen at Trump rallies, where people wearing QAnon shirts and hats are commonplace; at one recent rally in Las Vegas, the parents of a toddler in a QAnon shirt gamely posed for pictures with stranger after stranger. It was on display outside Walter Reed National Military Medical Center, where QAnon adherents gathered to support Trump after he was hospitalized with COVID-19. (Other QAnon adherents questioned whether the president had been hospitalized at all.)

Susan Cooper, 59, an insurance agent in nearby Calhoun, estimated that between 20% and 25% of her friends had bought into QAnon, though she had not. Others interviewed offered a similar assessment, and said it was a varied group young and old, male and female, poor and prosperous, urban and rural.

Its women that I talk to, Cooper said. These women are sharp ladies these women are women out of Atlanta, out of California, and friends of mine that are literally all over the country because of the company that I work with and they firmly believe this.

QAnon is spreading among evangelical Christians, too. The Biblical Recorder, a Southern Baptist newspaper in Cary, North Carolina, recently warned of its dangers. Christians should reject the movements fanatical and dangerous messages, wrote Seth Brown, the papers executive editor.

Many of the Republican Partys leaders and powerful donors are similarly concerned, as are a great many voters. Yet few high-profile Republicans have spoken out, demonstrating the thin line they are trying to walk between the moderate voters they need to win over and the members of their base who adore Trump.

Its a pro-Trump movement; QAnon is not of the Republican Party, said Dr. John Cowan, 45, a supporter of the president who ran in this years primary for a House seat representing northwest Georgia. It leaves no room between the president and Republican ideals and philosophy.

Cowan, a neurosurgeon, has seen up close the political impact of QAnon. He was trounced in the runoff by Marjorie Taylor Greene, 46, perhaps the most unabashed QAnon supporter running for Congress. She was caught on Facebook videos that surfaced earlier this year making offensive remarks about Black people, Jews and Muslims and openly courted the most extreme elements of the partys base during her primary campaign, presenting herself as the most loyal Trump supporter in the race.

Its corrupting the debate in the Republican Party, Cowan said of QAnon, because you cant separate yourself from the president in any way if you want to win.

It really is the religion of Trump devotees.

'God-tier genetics'The prophet of QAnon is Q, a purported government insider with a high-level security clearance who began posting cryptic messages in 2017 about the deep state trying to destroy the president. Followers pore over and interpret the postings known as Q drops and a core belief is that an apocalyptic showdown will smash the child-trafficking cabal and transform America. They call the transformation the Great Awakening.

At the center of the myth is Trump, often depicted as uniquely gifted with the abilities and fortitude needed to save America. The portrayal is taken straight out of his own playbook. From the moment he accepted the Republican nomination in 2016 and declared, I alone can fix it, to his claim earlier this month that catching the coronavirus was a blessing from God allowing him to stumble upon a miracle cure, the president has sought to present himself as a singular figure in history.

His most ardent supporters, especially QAnon believers, have amplified and further exaggerated his imagined powers. An entire cottage industry of online memes is devoted to photoshopping the president into famous great-man images, like the iconic painting of George Washington crossing the Delaware. It can now be found online with a grinning Trump pasted over the face of Americas first president.

At other times, Trump is treated as something close to divine. After the presidents coronavirus diagnosis, a prominent QAnon promoter, Brenden Dilley, told listeners of his radio show that Trump was blessed with god-tier genetics.

That same reverence was on display at Q Con Live!, a QAnon convention held in late August in Jacksonville, Florida. Much of the program was given over to extolling the accomplishments of Trump. The words glory and glorious came up often.

He has been gifted with abilities to do things that nobody else would even attempt or could actually accomplish, said David Martin, 58, a Navy veteran.

Martin, like most QAnon supporters, was certain the movement had the presidents support, a belief Trump and some of those around him appear to have encouraged well before his comments on Thursday night.

In August, the president described followers of QAnon several of whom have been charged with murder, domestic terrorism and planned kidnapping as people that love our country. His children and aides have shared social media posts related to the movement, their messaging becoming more explicit as Trumps poll numbers have dropped. His former national security adviser Michael Flynn a man seen in pro-Trump circles as a martyr unfairly persecuted in the Russia investigation posted a video this summer of himself taking what is known as the QAnon digital soldier oath.

The messages have been taken up by people like Bob Cox, 62, a retired construction worker who lives in Aragon, a small town about an hour outside Atlanta. He had little doubt that the political elite was rife with pedophiles, and he knew how he would handle them.

If people like that come in my neighborhood, I will shoot them, he said. I will absolutely do it.

But he was banking on Trump to take care of the problem first.

All this stuff is getting started through Soros, Cox added. He needs to be considered an enemy of the state, and Trump is on top of that. He knows.

QAnon countryThey began streaming into the Republican Party office in Dalton the self-described Carpet Capital of the World, a city of nearly 34,000 about 1.5 hours from Atlanta around dusk on a warm September day, husbands and wives, small groups of friends, young Republicans aspiring to careers in politics. They had come to see Marjorie Taylor Greene.

She is one of the more than dozen Republicans running for Congress who have signaled some degree of support for QAnon. Most are almost certain to be defeated in November, like Jo Rae Perkins, the long-shot Senate candidate in Oregon who posted a video in May declaring, I stand with Q and the team, and followed up in June with another video of herself taking the QAnon digital soldier oath. Others have a chance to win, including Lauren Boebert, who defeated a five-term Republican incumbent in a sprawling district in Colorado.

But it is Greene, alone among QAnon candidates, who is considered a near-lock to win a seat in Congress, and her campaign has turned Georgias 14th Congressional District into a ground zero of sorts for the transformation of QAnon into a political movement. She is, after all, the candidate who called QAnon a once-in-a-lifetime opportunity to take this global cabal of Satan-worshipping pedophiles out.

That might be a hindrance elsewhere, but not here. In this district, it can have benefits, said Kyer, the local party vice chairman.

Greenes district, which stretches from the northern exurbs of Atlanta all the way to the Tennessee border, is overwhelmingly white and Republican. Trump won upward of 70% of the vote in most parts of the district in 2016. Incomes in many areas are far below the national average, and railing against immigrants and foreign manufacturing plays well here. So does QAnon.

Were all aware of that pedophilia stuff, Kyer explained. But its also about how theyve the elites, that is been getting us into wars, just abusing power, taking advantage of the common middle-class people. It really hits home with a lot of people, whether they know all the details or not.

If Kyer was unsure about what he believed, others at the meeting were far more certain. Among those who subscribed to QAnon the crowd appeared to be split evenly between believers and nonbelievers many said they had learned about the movement from social media, and they ran the gamut from young digital natives to retirees who spent their days on Facebook, staying connected with old friends and being bombarded by disinformation.

Greta Hollis, 63, was typical. Though she had always considered herself a Republican, she said, politics had never much interested her. She saw Washington as a place where everyone was hustling to make a buck, not trying to help ordinary people. Then Trump ran for president, and said he was doing it to help people like her. She believed him.

She used to think greed was the driving force in politics. But how much money can somebody need? Hollis said. The more that greed and the money didnt make sense, I knew there had to be something else.

QAnon, she said, showed her what that was, and explained why Trump was facing so much resistance from Democrats and even some Republicans. All the pedophilia, all that kind of thing, the politics are so deep into that, I believe that, she said.

Then there were people like Putnam, the party chairwoman, who is in her 70s. She has served the local Republican Party in some capacity for most of the past 30 years. Her views, Putnam said, have evolved with the party, but she added, Ive always been a true conservative.

She acknowledged that meant something different back when she was a girl. There wouldnt be that much difference between Dwight Eisenhower and any of the Democrats, she said. And even going back to John Kennedy, even though he was a Democrat and everyone knew that he was more liberal than the conservative Republican, still his political policies were not so drastically different.

In her estimation, what changed was the proliferation of news sources on the internet peoples eyes began to be open to what was really happening and, most recently, Trumps decision to run for president.

Once he came down the escalator and announced his candidacy, people knew from the beginning he would be different, Putnam said. He couldnt be bought; he doesnt take his salary. So he cant be manipulated or controlled by financial contributions. Hes his own man.

She, too, was drawn to QAnon after seeing the resistance to Trump in Washington.

People know theres more going on than the public is aware of, she said. Donald Trump is trying to expose all of the corruption.

Greene, for her part, does her best to play it straight, now that she is in a general election, facing a somewhat broader ideological array of voters. Her stump speech makes no mention of QAnon or shadowy suspicions, and there is little hint of the unhinged conspiracy theorist that she was portrayed as by her opponents in the primary.

A political novice who declined an interview request, Greene knows how to work a crowd like a veteran. She cracks jokes and dispenses with any trappings of formality. Most important, she leaves little doubt where she stands on Trump.

After getting up to speak in Dalton, the first thing she did was push aside the lectern and replace it with a cardboard cutout of the president.

I just love this guy, she said.

Continue reading here:
Republican voters are taking a radical internet conspiracy theory into the mainstream - Economic Times

Recommendation and review posted by Bethany Smith

The awarding of this year's Nobel Prize for Chemistry to Jennifer Doudna and Emmanuelle Charpentier has been heralded as an incredible step forward for women. For the first time, two female scientists have been honored for an accomplishment without being accompanied by a man.

Also being heralded is the incredible potential of Doudna and Charpentier's gene-editing technology, CRISPR. Announcing the award, the Secretary-General of the Swedish Royal Academy of Science gushed, "This year's prize is about rewriting the code of life."

Doudna has used similar language to describe CRISPR technology, stating "the genome would become as malleable as a piece of literary prose at the mercy of an editor's red pen." And, so far, congratulations and praise from fellow scientists includes predictions and speculations that CRISPR will offer humanity new potential to combat all sorts of illnesses and make the world a better place.

Not covered in all the press announcing the award is the danger that CRISPR poses to us all. Consider, for example, the incident in which a Chinese scientist used CRISPR to edit the genome of embryos before implantation, a move that drew international criticism and gave the world a glimpse of just how this whole thing could go very wrong, was barely mentioned, if at all.

CRISPR has been likened to a computer mouse or pair of genetic scissors. One researcher described, "You can just point it at a place in the genome and you can do anything you want at that spot." Of course, it's not quite that simple. Still, the statement reveals the kind of hubris behind the drive to make this technology available, with virtually no ethical guidelines in place.

There seems to be this assumption that, of course, scientists and researchers will "play nice" with the power CRISPR offers. History, of course, tells us that it's nearly impossible to resist the temptation to "play God" instead. And that never ends well.

Earlier this year, a team of researchers at the Francis Crick Institute in London used CRISPR to edit 18 donated human embryos, supposedly to study "the role of a particular gene in the earliest stages of human development." The Crick Institute team did everything by the book. Still, despite their best efforts, around half of the embryos contained what researchers called "major unintended edits." "Major unintended edits" is Newspeak for serious genetic damage, the kind of damage that can lead to birth defects or future medical issues, like cancer.

How did this happen when researchers were so careful to play by the rules? One genetics researcher put it this way: "You're affecting so much of the DNA around the gene you're trying to edit that you could be inadvertently affecting other genes and causing problems."

If these sorts of problems come with researchers playing by the rules and acting out of good intention, what might happen when research is driven by greed or is done in some unregulated environment? Seeing the results from the Crick Institute researchers prompted one molecular biologist to call for "a restraining order for all genome editors to stay the living daylights away from embryo editing."

Now, a few months later, the Nobel Prize committee has put its official stamp of approval on the technology and its promise to "rewrite the code of life." Absent regulations with real teeth, there will be no restraining order coming.

There's an ironic connection here to historic origins of the Nobel Prize. Alfred Nobel was the inventor of dynamite. He hoped and intended for his invention to be used for blasting rocks apart. Instead, it was used to blast people apart.

When Alfred's brother died, a French newspaper, mistakenly believing that it was Alfred who had died, proclaimed "The Merchant of Death Is Dead!" Appalled by the reputation his invention brought to him, Nobel established the Nobel Prizes, including the Nobel Peace Prize, hoping his legacy would be a better world instead of death and suffering.

By awarding the prize to the inventors of CRISPR, the committee is repeating Nobel's history and turning his intentions on their head. Like dynamite, whatever legitimate potential CRISPR holds will operate alongside of even greater potential for harm. And it's not regulated anywhere near the degree that dynamite is.

From BreakPoint, Oct. 12, 2020; reprinted by permission of the Colson Center, http://www.breakpoint.org.

Read this article:
BreakPoint: Inventors of CRISPR win Nobel Prize, but should we 'rewrite the code of life'? - Chattanooga Times Free Press

Recommendation and review posted by Bethany Smith

Background

Observational studies have identified height as a strong risk factor for atrial fibrillation, but this finding may be limited by residual confounding. We aimed to examine genetic variation in height within the Mendelian randomization (MR) framework to determine whether height has a causal effect on risk of atrial fibrillation.

In summary-level analyses, MR was performed using summary statistics from genome-wide association studies of height (GIANT/UK Biobank; 693,529 individuals) and atrial fibrillation (AFGen; 65,446 cases and 522,744 controls), finding that each 1-SD increase in genetically predicted height increased the odds of atrial fibrillation (odds ratio [OR] 1.34; 95% CI 1.29 to 1.40; p = 5 10-42). This result remained consistent in sensitivity analyses with MR methods that make different assumptions about the presence of pleiotropy, and when accounting for the effects of traditional cardiovascular risk factors on atrial fibrillation. Individual-level phenome-wide association studies of height and a height genetic risk score were performed among 6,567 European-ancestry participants of the Penn Medicine Biobank (median age at enrollment 63 years, interquartile range 55-72; 38% female; recruitment 2008-2015), confirming prior observational associations between height and atrial fibrillation. Individual-level MR confirmed that each 1-SD increase in height increased the odds of atrial fibrillation, including adjustment for clinical and echocardiographic confounders (OR 1.89; 95% CI 1.50 to 2.40; p = 0.007). The main limitations of this study include potential bias from pleiotropic effects of genetic variants, and lack of generalizability of individual-level findings to non-European populations.

In this study, we observed evidence that height is likely a positive causal risk factor for atrial fibrillation. Further study is needed to determine whether risk prediction tools including height or anthropometric risk factors can be used to improve screening and primary prevention of atrial fibrillation, and whether biological pathways involved in height may offer new targets for treatment of atrial fibrillation.

Originally posted here:
Genetics of Height and Risk of Atrial Fibrillation: A Mendelian Randomization Study - DocWire News

Recommendation and review posted by Bethany Smith

As its cultivation partner, Pink Haze tapped Clade9 Los Angeles, the 2019 recipient of the prestigious Cannabis Business Awards for Lifetime Achievement in Cultivation. Clade9 produces some of the most sought-after genetics and indoor flower popular among cannabis connoisseurs.

Founders of Pink Haze, Patty Roe and Summer Edwards, entered the cannabis industry in 2016 through a medical cannabis delivery platform, where the majority of patients were women. Roe and Edwards felt their clients deserved a higher-quality experience, in both products and community, so they changed focus from delivery to brand development and founded Pink Haze.

"I am thrilled to launch a product that celebrates and empowers women. Pink Haze is here to offer the women we love and support a product worthy of their time, standards, and money," said Patty Roe, CEO. "We don't want people to just buy a joint, we want people to celebrate the freedom and acceptance that we now have with cannabis and feel a part of something bigger."

Pink HazeFemale-owned and led luxury cannabis brand, Pink Haze, LLC, was founded by Patty Roe, whose diverse career took her from the securities industry, to Capitol Hill, to founding a successful multi-million dollar marketing firm. In 2016, she walked away and committed her future to cannabis and empowering women.

Co-founder Summer Edwards, is a lifestyle-branding expert and international award-winning photographer. Edwards built a successful photography business in Arizona and was named one of Phoenix's top photojournalist portrait photographers. Edwards was also a roller derby legend, playing for nearly ten years.

Founded in 2017, Pink Haze has launched their first round of funding, seeking $1.5 million utilizing convertible notes. Interested investors should contact Patty Roe.

Pink Sesh SocietyUnique among any other products in the market, Pink Haze is an important part of Pink Sesh Society, which Roe and Edwards founded early in the development of Pink Haze. What began as a casual monthly gathering of diverse Southern California women celebrating cannabis, rapidly became a life changing membership organization that now boasts 20,000 organic Instagram followers and a national following.

The unique relationship between Pink Sesh and Pink Haze promises to elevate Pink Haze's popularity in the market by elevating a woman's cannabis experience through community.

Pink Haze Instagram: https://www.instagram.com/thepinkhaze/

Pink Sesh Instagram: https://www.instagram.com/thepinksesh/

Pink Sesh TikTok: https://www.tiktok.com/@pinksesh?lang=en

SOURCE Pink Haze

Home

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Women Rise Above with Launch of Pink Haze - PRNewswire

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Most mammalian chromosomes dictate their sex-identity with X and Y chromosomes. XX is female, XY is male, including in humans. However, in nearly six species of moles, XX females have been found with a hybrid of ovaries and testes known as ovotestes.

The testes arent fully functional. They cannot produce any sperm but they can release very high levels of testosterone (male-associated hormone). As a result, these moles become excellent diggers which helps them with their underground life.

The puzzle for scientists is how these male reproductive tissues are being formed in female moles even without the Y-chromosome. The answer is probably to look at the regions which control the genes instead of the genes themselves. The study was published in journal Science.

The female Iberian mole can be considered as intersex, as it has both male and female reproductive tissue. However, she develops a vagina only during the mating season and has functional female organs.

With most animals, males fertilize the egg produced by a female. However, 1% of humans can be born intersex. Other species like snails, earthworms, slugs etc can be hermaphrodite i.e. fully developed male and female reproductive parts.

The mole, however, feels different from them all, she has a male-looking external genital with a clitoris that looks like a penis. And for the most part of her life, the vaginal canal has no opening. While the testosterone production low in mating season, it can be higher than XY males for the rest of the year in these intersex moles.

At a certain point, sexual development usually progresses in one direction or another, male or female, explained Daro Lupiez, Geneticist at Max Planck Institute. However, they want to study how the evolution of these animals modulates sexual behaviour. The team theorizes that the ovotestes suggest some other gene must be active in the females, one that is not found on Y chromosome. The gene responsible for producing male hormones is CYP17A1.

They observed that it was present three times in the female moles genome instead of one. The triplication appends additional regulatory sequences to the gene which ultimately leads to an increased production of male sex hormones in the ovotestes of female moles, especially more testosterone, explained Francisca Martinez. She is the lead author of the study from the Institute for Medical Genetics and Human Genetics in Berlin.

Studies like these are important to normalise the existence of intersex individuals, even in humans, who are generally pathologized.

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Female Moles Have 'Ovotestes' that Produce Testosterone That Make Them Excellent Diggers - News18

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AVALONThe Catalina Island Conservancy has been working to expand the bison herd on the island.

Two pregnant female bison will arrive on the island in December and are expected to give birth in the spring. The new additions come from the Laramie Foothills Bison Conservation Herd and will integrate into Catalina Islands free-ranging bison herd of approximately 100.

The Conversancy said the new additions will supplement the genetic diversity of the current bison herd on Catalina Island with the valuable genetics of heritage bison.

The Laramie Foothills Bison Conservation Herd is managed by Colorado State University, the City of Fort Collins, Colorado, and Larimer County. The herd was established with nine adult females and one male calf in November 2015. It has now grown to over 100 bison, which has made it possible to share bison with tribal and conservation herds across the country.

According to the Conservancy, the bison have valuable genetics from the Yellowstone

National Park Herd and, thanks to science implemented at CSU by Assistant Professor Jennifer

Barfield and her team, the animals are also disease-free.

We look forward to watching our animals find a new home with the herd on Catalina Island, where they can contribute to the growth of a truly unique and iconic herd, Barfield, a reproductive physiologist, said in a released statement.

Bison have freely roamed Catalina Island since 1924 when 14 bison were brought to the Island for the filming of an adaptation of a Zane Grey novel, believed to be The Vanishing American. The Conservancy said bison have played a significant role in the cultural heritage of Catalina Island and will be roaming the island far into the future.

The unique opportunity to see American bison on Catalina Island brings wildlife lovers from around the world to learn about a species they might otherwise not have a chance to see roam, said Catalina Island Conservancy President & CEO Tony Budrovich. While here, they also learn about Catalinas endemic species, special Mediterranean climate and importance of conservation.

Those wishing to see bison on the island can do so through the Conservancys Eco Tour. The Conversancy reminds everyone that bison are wild animals and people should stay at least 125 feet away from bison at all times.

View original post here:
New bison to join Catalina Island herd The Log - The Log Newspaper

Recommendation and review posted by Bethany Smith

ourtesy of Catalina Island Conservancy

Bison have played a significant role in the cultural heritage of Catalina Island for nearly 100 years and will be roaming Catalina Island far into the future. Catalina Island Conservancy is working with the Laramie Foothills Bison Conservation herd to bring two pregnant female bison to Catalina Island. The new additions will arrive in early December and supplement the genetic diversity of the current bison herd on Catalina Island with the valuable genetics of heritage bison.

The herd managed by Colorado State University, the city of Fort Collins, Colorado, and Larimer County was established with nine adult females and one male calf in November 2015. It has now grown to over 100 bison, which has made it possible to share bison with tribal and conservation herds across the country. The bison have valuable genetics from the Yellowstone National Park herd and, thanks to science implemented at CSU by Assistant Professor Jennifer Barfield and her team, the animals are also disease-free.

We are proud to continue our mission of collaborating with conservationists through this new partnership with Catalina Island Conservancy, said Barfield, a reproductive physiologist. We look forward to watching our animals find a new home with the herd on Catalina Island, where they can contribute to the growth of a truly unique and iconic herd.

Bison have freely roamed Catalina Island since 1924. Fourteen bison were brought to the island for the filming of an adaptation of a Zane Grey novel, believed to be The Vanishing American. There are currently approximately 100 bison on Catalina Island. The new animals will integrate into Catalina Islands free-ranging bison herd in December and are expected to give birth in the spring.

With goals of maintaining the health of the land and providing public benefit, Catalina Island Conservancy maintains its three-part mission of conservation, education and recreation. The bison population is a key example of this delicate balance, said Tony Budrovich, Conservancy president and CEO . The unique opportunity to see American bison on Catalina Island brings wildlife lovers from around the world to learn about a species they might otherwise not have a chance to see roam. While here, they also learn about Catalinas endemic species, special Mediterranean climate and importance of conservation.

With its location close to urban areas, Catalina provides a gateway to nature for a diverse population to experience and learn about wildlife and nature just steps away from home. The best way to view bison is through a Conservancy Eco Tour. Bison are wild animals. People should stay at least 125 feet away from bison at all times.

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More bison to join island herd - The Catalina Inslader

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The latest adventure in food enhancement is CRISPR (e.g., clustered regularly interspaced short palindromic repeats/Cas9) gene-editing technology. It potentially has many major implications for enhanced global agriculture and much needed improvements in food security. CRISPR and gene editing tools simultaneously represents an extensive legal and regulatory challenge and additionally, a monumental scientific opportunity for the global food industry. With the development of genome editing technologies, the possibility of directly targeting and subsequently modifying genomic sequences in plants is intriguing. Genome editing can extend our ability to develop an extraordinary potential in applied biotechnology and its effects on increased world food production.

An important concept to the understanding of CRISPR/Cas came from scientific observations that the prokaryote repeat cluster (a family of DNA sequences found in the genomes ofprokaryoticorganisms such as bacteria and archaea) was incorporated into a set of homologous genes (having the same relation/structure or relative position) that make up CRISPR-associated systems orCasgenes.

TheCasproteins show nuclease and helicase motifs (a linkage that is found in a great many other DNA processing enzymes) which suggests an important role of the CRISPR loci. The development of programmable nucleases (e.g., clustered regularly interspaced short palindromic repeat (CRISPR)Cas-associated nucleases, zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs)) has expedited the ability to improve the field of gene editing and subsequently potentially improve food production. CRISPR/Cas gene editing technology can potentially increase plant/crop yields and quality, plant drought resistance, herbicide and insecticide resistance, improved food safety and security, enhance the removal of antibiotic resistance (AMR), improve product shelf life and it can potentially accelerate the process of plant domestication.

Read more at Michigan State University (Scott Haskell)

Read more:
CRISPR and our food supply: What's next in feeding the world? - hortidaily.com

Recommendation and review posted by Bethany Smith

We think that its fair to say that the possibility of finding fantastic multi-year winners is what motivates many investors. Mistakes are inevitable, but a single top stock pick can cover any losses, and so much more. Take, for example, the CRISPR Therapeutics AG (NASDAQ:CRSP) share price, which skyrocketed 424% over three years. In more good news, the share price has risen 1.7% in thirty days.

View our latest analysis for CRISPR Therapeutics

We dont think that CRISPR Therapeutics modest trailing twelve month profit has the markets full attention at the moment. We think revenue is probably a better guide. As a general rule, we think this kind of company is more comparable to loss-making stocks, since the actual profit is so low. For shareholders to have confidence a company will grow profits significantly, it must grow revenue.

Over the last three years CRISPR Therapeutics has grown its revenue at 101% annually. Thats well above most pre-profit companies. And its not just the revenue that is taking off. The share price is up 74% per year in that time. Despite the strong run, top performers like CRISPR Therapeutics have been known to go on winning for decades. So wed recommend you take a closer look at this one, or even put it on your watchlist.

You can see below how earnings and revenue have changed over time (discover the exact values by clicking on the image).

CRISPR Therapeutics is well known by investors, and plenty of clever analysts have tried to predict the future profit levels. So it makes a lot of sense to check out what analysts think CRISPR Therapeutics will earn in the future (free analyst consensus estimates)

Pleasingly, CRISPR Therapeutics total shareholder return last year was 163%. So this years TSR was actually better than the three-year TSR (annualized) of 74%. The improving returns to shareholders suggests the stock is becoming more popular with time. While it is well worth considering the different impacts that market conditions can have on the share price, there are other factors that are even more important. For example, weve discovered 2 warning signs for CRISPR Therapeutics that you should be aware of before investing here.

But note: CRISPR Therapeutics may not be the best stock to buy. So take a peek at this free list of interesting companies with past earnings growth (and further growth forecast).

Please note, the market returns quoted in this article reflect the market weighted average returns of stocks that currently trade on US exchanges.

PromotedIf youre looking to trade CRISPR Therapeutics, open an account with the lowest-cost* platform trusted by professionals, Interactive Brokers. Their clients from over 200 countries and territories trade stocks, options, futures, forex, bonds and funds worldwide from a single integrated account.

This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned. *Interactive Brokers Rated Lowest Cost Broker by StockBrokers.com Annual Online Review 2020

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com.

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Introducing CRISPR Therapeutics (NASDAQ:CRSP), The Stock That Soared 424% In The Last Three Years - Simply Wall St

Recommendation and review posted by Bethany Smith

LOS ANGELES, United States:The report titledGlobal CRISPR And CRISPR-Associated (Cas) Genes Marketis one of the most comprehensive and important additions to QY Researchs archive of market research studies. It offers detailed research and analysis of key aspects of the global CRISPR And CRISPR-Associated (Cas) Genes market. The market analysts authoring this report have provided in-depth information on leading growth drivers, restraints, challenges, trends, and opportunities to offer a complete analysis of the global CRISPR And CRISPR-Associated (Cas) Genes market. Market participants can use the analysis on market dynamics to plan effective growth strategies and prepare for future challenges beforehand. Each trend of the global CRISPR And CRISPR-Associated (Cas) Genes market is carefully analyzed and researched about by the market analysts.The market analysts and researchers have done extensive analysis of the global CRISPR And CRISPR-Associated (Cas) Genes market with the help of research methodologies such as PESTLE and Porters Five Forces analysis. They have provided accurate and reliable market data and useful recommendations with an aim to help the players gain an insight into the overall present and future market scenario. The CRISPR And CRISPR-Associated (Cas) Genes report comprises in-depth study of the potential segments including product type, application, and end user and their contribution to the overall market size.

In addition, market revenues based on region and country are provided in the CRISPR And CRISPR-Associated (Cas) Genes report. The authors of the report have also shed light on the common business tactics adopted by players. The leading players of the global CRISPR And CRISPR-Associated (Cas) Genes market and their complete profiles are included in the report. Besides that, investment opportunities, recommendations, and trends that are trending at present in the global CRISPR And CRISPR-Associated (Cas) Genes market are mapped by the report. With the help of this report, the key players of the global CRISPR And CRISPR-Associated (Cas) Genes market will be able to make sound decisions and plan their strategies accordingly to stay ahead of the curve.

Competitive landscape is a critical aspect every key player needs to be familiar with. The report throws light on the competitive scenario of the global CRISPR And CRISPR-Associated (Cas) Genes market to know the competition at both the domestic and global levels. Market experts have also offered the outline of every leading player of the global CRISPR And CRISPR-Associated (Cas) Genes market, considering the key aspects such as areas of operation, production, and product portfolio. Additionally, companies in the report are studied based on the key factors such as company size, market share, market growth, revenue, production volume, and profits.

Key Players Mentioned in the Global CRISPR And CRISPR-Associated (Cas) Genes Market Research Report:, Caribou Biosciences, Addgene, CRISPR THERAPEUTICS, Merck KGaA, Mirus Bio LLC, Editas Medicine, Takara Bio USA, Thermo Fisher Scientific, Horizon Discovery Group, Intellia Therapeutics, GE Healthcare Dharmacon

Get Full PDF Sample Copy of Report: (Including Full TOC, List of Tables & Figures, Chart)

http://qyresearch.com/sample-form/form/1514308/global-crispr-and-crispr-associated-cas-genes-industry

Segmental Analysis

The report has classified the globalCRISPR And CRISPR-Associated (Cas) Genesindustry into segments including product type and application. Every segment is evaluated based on growth rate and share. Besides, the analysts have studied the potential regions that may prove rewarding for theCRISPR And CRISPR-Associated (Cas) Genes manufacturers in the coming years. The regional analysis includes reliable predictions on value and volume, thereby helping market players to gain deep insights into the overallCRISPR And CRISPR-Associated (Cas) Genesindustry.

GlobalCRISPR And CRISPR-Associated (Cas) Genes Market Segment By Type:

, the CRISPR And CRISPR-Associated (Cas) Genes market is segmented into, Genome Editing, Genetic engineering, gRNA Database/Gene Librar, CRISPR Plasmid, Human Stem Cells, Genetically Modified Organisms/Crops, Cell Line Engineering

GlobalCRISPR And CRISPR-Associated (Cas) Genes Market Segment By Application:

Biotechnology Companies, Pharmaceutical Companies, Academic Institutes, Research and Development Institutes

The CRISPR And CRISPR-Associated (Cas) Genes Market report has been segregated based on distinct categories, such as product type, application, end user, and region. Each and every segment is evaluated on the basis of CAGR, share, and growth potential. In the regional analysis, the report highlights the prospective region, which is estimated to generate opportunities in the global CRISPR And CRISPR-Associated (Cas) Genes market in the forthcoming years. This segmental analysis will surely turn out to be a useful tool for the readers, stakeholders, and market participants to get a complete picture of the global CRISPR And CRISPR-Associated (Cas) Genes market and its potential to grow in the years to come.

Key questions answered in the report:

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Table of Contents:

Table of Contents 1 Report Overview1.1 Research Scope1.2 Top CRISPR And CRISPR-Associated (Cas) Genes Manufacturers Covered: Ranking by Revenue1.3 Market Segment by Type

1.3.1 Global CRISPR And CRISPR-Associated (Cas) Genes Market Size by Type: 2015 VS 2020 VS 2026 (US$ Million)

1.3.2 Genome Editing

1.3.3 Genetic engineering

1.3.4 gRNA Database/Gene Librar

1.3.5 CRISPR Plasmid

1.3.6 Human Stem Cells

1.3.7 Genetically Modified Organisms/Crops

1.3.8 Cell Line Engineering1.4 Market Segment by Application

1.4.1 Global CRISPR And CRISPR-Associated (Cas) Genes Consumption by Application: 2015 VS 2020 VS 2026

1.4.2 Biotechnology Companies

1.4.3 Pharmaceutical Companies

1.4.4 Academic Institutes

1.4.5 Research and Development Institutes1.5 Study Objectives1.6 Years Considered 2 Global Market Perspective2.1 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue (2015-2026)

2.1.1 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue (2015-2026)

2.1.2 Global CRISPR And CRISPR-Associated (Cas) Genes Sales (2015-2026)2.2 CRISPR And CRISPR-Associated (Cas) Genes Market Size across Key Geographies Worldwide: 2015 VS 2020 VS 2026

2.2.1 Global CRISPR And CRISPR-Associated (Cas) Genes Sales by Regions (2015-2020)

2.2.2 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue by Regions (2015-2020)2.3 Global Top CRISPR And CRISPR-Associated (Cas) Genes Regions (Countries) Ranking by Market Size2.4 CRISPR And CRISPR-Associated (Cas) Genes Industry Trends

2.4.1 CRISPR And CRISPR-Associated (Cas) Genes Market Top Trends

2.4.2 Market Drivers

2.4.3 CRISPR And CRISPR-Associated (Cas) Genes Market Challenges 2.4.4 Porters Five Forces Analysis

2.4.5 Primary Interviews with Key CRISPR And CRISPR-Associated (Cas) Genes Players: Views for Future 3 Competitive Landscape by Manufacturers3.1 Global Top CRISPR And CRISPR-Associated (Cas) Genes Manufacturers by Sales (2015-2020)

3.1.1 Global CRISPR And CRISPR-Associated (Cas) Genes Sales by Manufacturers (2015-2020)

3.1.2 Global CRISPR And CRISPR-Associated (Cas) Genes Sales Market Share by Manufacturers (2015-2020)

3.1.3 Global 5 and 10 Largest Manufacturers by CRISPR And CRISPR-Associated (Cas) Genes Sales in 20193.2 Global Top Manufacturers CRISPR And CRISPR-Associated (Cas) Genes by Revenue

3.2.1 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue by Manufacturers (2015-2020)

3.2.2 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue Share by Manufacturers (2015-2020)

3.2.3 Global CRISPR And CRISPR-Associated (Cas) Genes Market Concentration Ratio (CR5 and HHI)3.3 Global Top Manufacturers by Company Type (Tier 1, Tier 2 and Tier 3) (based on the Revenue in CRISPR And CRISPR-Associated (Cas) Genes as of 2019)3.4 Global CRISPR And CRISPR-Associated (Cas) Genes Average Selling Price (ASP) by Manufacturers3.5 Key Manufacturers CRISPR And CRISPR-Associated (Cas) Genes Plants/Factories Distribution and Area Served3.6 Date of Key Manufacturers Enter into CRISPR And CRISPR-Associated (Cas) Genes Market3.7 Key Manufacturers CRISPR And CRISPR-Associated (Cas) Genes Product Offered 3.8 Mergers & Acquisitions, Expansion Plans 4 Market Size by Type4.1 Global CRISPR And CRISPR-Associated (Cas) Genes Historic Market Review by Type (2015-2020)

4.1.2 Global CRISPR And CRISPR-Associated (Cas) Genes Sales Market Share by Type (2015-2020)

4.1.3 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue Market Share by Type (2015-2020)

4.1.4 CRISPR And CRISPR-Associated (Cas) Genes Price by Type (2015-2020)4.1 Global CRISPR And CRISPR-Associated (Cas) Genes Market Estimates and Forecasts by Type (2021-2026)

4.2.2 Global CRISPR And CRISPR-Associated (Cas) Genes Sales Forecast by Type (2021-2026)

4.2.3 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue Forecast by Type (2021-2026)

4.2.4 CRISPR And CRISPR-Associated (Cas) Genes Price Forecast by Type (2021-2026) 5 Global CRISPR And CRISPR-Associated (Cas) Genes Market Size by Application5.1 Global CRISPR And CRISPR-Associated (Cas) Genes Historic Market Review by Application (2015-2020)

5.1.2 Global CRISPR And CRISPR-Associated (Cas) Genes Sales Market Share by Application (2015-2020)

5.1.3 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue Market Share by Application (2015-2020)

5.1.4 CRISPR And CRISPR-Associated (Cas) Genes Price by Application (2015-2020)5.2 Global CRISPR And CRISPR-Associated (Cas) Genes Market Estimates and Forecasts by Application (2021-2026)

5.2.2 Global CRISPR And CRISPR-Associated (Cas) Genes Sales Forecast by Application (2021-2026)

5.2.3 Global CRISPR And CRISPR-Associated (Cas) Genes Revenue Forecast by Application (2021-2026)

5.2.4 CRISPR And CRISPR-Associated (Cas) Genes Price Forecast by Application (2021-2026) 6 North America6.1 North America CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Company6.2 North America CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Type6.3 North America CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Application6.4 North America CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Countries

6.4.1 North America CRISPR And CRISPR-Associated (Cas) Genes Sales by Countries

6.4.2 North America CRISPR And CRISPR-Associated (Cas) Genes Revenue by Countries

6.4.3 U.S.

6.4.4 Canada 7 Europe7.1 Europe CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Company7.2 Europe CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Type7.3 Europe CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Application7.4 Europe CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Countries

7.4.1 Europe CRISPR And CRISPR-Associated (Cas) Genes Sales by Countries

7.4.2 Europe CRISPR And CRISPR-Associated (Cas) Genes Revenue by Countries

7.4.3 Germany

7.4.4 France

7.4.5 U.K.

7.4.6 Italy

7.4.7 Russia 8 Asia Pacific8.1 Asia Pacific CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Company8.2 Asia Pacific CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Type8.3 Asia Pacific CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Application8.4 Asia Pacific CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Regions

8.4.1 Asia Pacific CRISPR And CRISPR-Associated (Cas) Genes Sales by Regions

8.4.2 Asia Pacific CRISPR And CRISPR-Associated (Cas) Genes Revenue by Regions

8.4.3 China

8.4.4 Japan

8.4.5 South Korea

8.4.6 India

8.4.7 Australia

8.4.8 Taiwan

8.4.9 Indonesia

8.4.10 Thailand

8.4.11 Malaysia

8.4.12 Philippines

8.4.13 Vietnam 9 Latin America9.1 Latin America CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Company9.2 Latin America CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Type9.3 Latin America CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Application9.4 Latin America CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Countries

9.4.1 Latin America CRISPR And CRISPR-Associated (Cas) Genes Sales by Countries

9.4.2 Latin America CRISPR And CRISPR-Associated (Cas) Genes Revenue by Countries

9.4.3 Mexico

9.4.4 Brazil

9.4.5 Argentina 10 Middle East and Africa10.1 Middle East and Africa CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Type10.2 Middle East and Africa CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Application10.3 Middle East and Africa CRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by Countries

10.3.1 Middle East and Africa CRISPR And CRISPR-Associated (Cas) Genes Sales by Countries

10.3.2 Middle East and Africa CRISPR And CRISPR-Associated (Cas) Genes Revenue by Countries

10.3.3 Turkey

10.3.4 Saudi Arabia

10.3.5 U.A.E 11 Company Profiles11.1 Caribou Biosciences

11.1.1 Caribou Biosciences Corporation Information

11.1.2 Caribou Biosciences Business Overview and Total Revenue (2019 VS 2018)

11.1.3 Caribou Biosciences CRISPR And CRISPR-Associated (Cas) Genes Sales, Revenue, Average Selling Price (ASP) and Gross Margin (2015-2020)

11.1.4 Caribou Biosciences CRISPR And CRISPR-Associated (Cas) Genes Products and Services

11.1.5 Caribou Biosciences SWOT Analysis

11.1.6 Caribou Biosciences Recent Developments11.2 Addgene

11.2.1 Addgene Corporation Information

11.2.2 Addgene Business Overview and Total Revenue (2019 VS 2018)

11.2.3 Addgene CRISPR And CRISPR-Associated (Cas) Genes Sales, Revenue, Average Selling Price (ASP) and Gross Margin (2015-2020)

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CRISPR And CRISPR-Associated (Cas) Genes Market Break Down by Top Companies, Countries, Applications, Challenges, Opportunities and Forecast by...

Recommendation and review posted by Bethany Smith

CRISPR Therapeutics (NASDAQ:CRSP) and Vertex Pharmaceuticals Incorporated (NASDAQ:VRTX) have announced that the European Medicines Agency has granted their experimental, autologous, ex vivo CRISPR/Cas9 gene-edited therapy, CTX001 Priority Medicines designation. The therapy has been granted PRIME designation for severe sickle cell disease treatment.

The PRIME designation is a regulatory mechanism that offers early and proactive support to promising medicines developers to enhance development plans. Also, it accelerates the evaluation of medicines under development to reach patients as soon as possible. PRIMEs objective is to ensure patients benefit fasters from new proprietary therapies that have shown the potential of addressing a significant unmet medical need. The companies received the PRIME designation based on data from their on-going phase 1/2 study of CTX001 in treating severe sickle cell disease patients.

CTX001 is currently being investigated to treat patients with severe SCD or transfusion-dependent beta-thalassemia, whereby hematopoietic stem cells are purposed to produce high fetal hemoglobin levels in red cells. HbF is an oxygen-carrying hemoglobin form present naturally at birth, which later switches to adult hemoglobin form. HbF elevation by CTX001 can potentially alleviate transfusion requirements for TDT patients and minimize painful and devastating sickle crises in patients with SCD.

So far, CTX001 has received Regenerati9ve Medicine Advanced Therapy (RMAT), Orphan Drug Designation, and Fast Track designation from the FDA. Also, CTX001 has Orphan Drug Designation from the European Commission for SCD and TDT.

CRISPR Therapeutics and Vertex are developing CTX001 under a co-development and co-commercialization agreement. So far, CTX001 is the most progressive gene editing therapy under development for SCD and TDT. The companies entered a strategic collaboration agreement in 2015 intending to use CRISPR/Cas9 to develop and discover novel therapies for the treatment of underlying genetic causes of diseases. CTX001 is the first joint treatment to emerge from the collaboration, and all development costs and profits will be shared.

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CRISPR Therapeutics (NASDAQ:CRSP) and Vertex (NASDAQ:VRTX) Receive Priority Medicines (PRIME) Designation From EMA For CTX001 In SCD - BP Journal

Recommendation and review posted by Bethany Smith

A one-year-old girl donated her bone marrow to her brother. (Representational)

A one-year-old girl, conceived by her parents through IVF technology specifically for the purpose of donating her bone marrow to their thalassemic son, has succeeded in saving her six-year-old brother's life.

Baby Kavya was born a year ago through In-Vitro Fertilisation (IVF) technique in Ahmedabad, under the concept known as "saviour sibling".

Her bone marrow was successfully transplanted to her brother Abhijeet Solanki in March this year and the boy is now "risk-free", doctors said on Thursday.

Abhijeet, the second child of Sahdev Singh Solanki and Alpa Solanki, was diagnosed with Thalassemia-major, a blood disorder, and was dependent on blood transfusion every month, they said.

Thalassemia-major patients require frequent blood transfusions and their life expectancy is also less.

His parents were advised bone marrow transplant as the last resort to treat the child, but they could not find the required HLA (human leukocyte antigen) match.

"Due to unavailability of matching HLA donors for the transplant, we opted for IVF with HLA matching," city-based Nova IVF Fertility's medical director Dr Manish Banker told PTI.

This process of HLA typing is an established method for conceiving a child, who may donate cord blood or hematopoietic stem cells for transplantation to save a sibling with a critical illness.

Abhijeet's father approached Mr Banker after he found that the bone marrow of his family members, including the boy's elder sister, was not matching.

"Bone marrow transplant from an HLA-identical donor is the best therapeutic option for thalassemia major patients. We took the challenge and created a healthy savior sibling to save her elder brother," Mr Banker said.

With the help of IVF, Abhijeet's mother delivered a healthy baby girl Kavya a year ago, who was found to be the HLA match for the sibling.

In March this year, after Kavya gained the required weight, a successful bone marrow transplant was done for Abhijeet at the CIMS Hospital, Mr Banker said.

"Now, Abhijeet is risk-free and doesn't require blood transfusion," Mr Banker said.

"This is the first case in India when an HLA matching baby was born through IVF specifically to save the thalassemia-major sibling," he said.

The siblings' father, who himself researched well about this technique, thanked Mr Banker and other expert doctorsfor saving his son.

Excerpt from:
Child Conceived To Donate Bone Marrow Saves 6-Year-Old Brother's Life - NDTV

Recommendation and review posted by Bethany Smith

India just conducted its first successful experiment with savior sibling therapy, in which a baby was conceived through in-vitro fertilization for the purposes of donating bone marrow to an older ailing brother struggling with thalassemia, a condition characterized by low levels of hemoglobin in the blood that requires frequent blood transfusions. While the doctors involved in the therapy celebrated their success this week, some on social media challenged the ethics of such a therapy, in which a baby was essentially birthed to save her sibling.

In this case, the child with the genetic disorder needed a bone marrow transplant to cure his disease, and the chances of a successful cure are higher if coming from a person whose proteins (human leukocyte antigens, or HLA) exactly match those of the child. None of the childs existing family members was a match, further complicating the process of getting a bone marrow transplant an already difficult process to execute. The parents, in an effort to create a perfect bone marrow match for their child, underwent three cycles of in-vitro fertilization, out of which 18 embryos were created, and one perfectly matched that of the child, and was disease-free, using a technique called pre-implantation genetic diagnosis (PGD). The embryo was then implanted in the mothers uterus, carried to term, and a baby girl was born.

We had to wait for the baby to grow. She had to weigh 10 kg before we could draw bone marrow, Deepa Trivedi, program director of Sankalp Bone Marrow Unit in Ahmedabad, told The Hindu. Its been approximately seven months since the transplant, and the older sibling has not needed any more blood transfusions, indicating he has been cured of his thalassemia, his doctors announced.

Savior sibling therapy has already been used in countries such as the United Kingdom, the U.S.A., New Zealand, and France. Its mainly used to cure genetic blood disorders in children, such as sickle cell anemia or as seen in the Indian case, thalassemia major. The main way this is done, which is a departure from the Indian case, is by harvesting stem cells from a newborns umbilical cord, which are then injected into the bone marrow of the sibling with the disease, a practice that works 90% of the time. In case it doesnt, doctors can take bone marrow from the savior sibling as they grow, in a process that is painful but not known to be dangerous.

Related on The Swaddle:

Designer Babies Are Far From Reality, Even After the Gene-Edited Babies in China

The first ethical concern with this practice is treating a baby as a source for spare parts, as a means to an end, as a commodity. A study of the bioethics of savior sibling therapy, published in the Journal of Medical Ethics, surmised that treating a baby as a means to an end was not by itself a concern that devalued the utility of savior sibling therapy, as long as theyre also treated as human beings. Bioethicists surmise that using cord blood, something that is frequently discarded after birth, cannot endanger a newborn, or prove to be an ethical quandary used against the therapy.

But what has happened in the most recent case in India actually complicates the issue, because its not the umbilical cord blood that was harvested from the savior sibling at birth, but bone marrow 10 months into her life, which makes her an organ donor. This traverses thorny territory, as governments strictly regulate organ donation by minors due to issues related to consent. Can a baby consent to donating bone marrow to their sibling, or a 10-year-old consent to donating a kidney to their parent? It depends on where the individual resides, and how old the person being asked to donate is. In India, for example, it was only recently that the Delhi High Court ruled that minors could donate organs or tissues, as long as the procedure didnt pose a danger to their lives, and only in exceptional circumstances. However, where minors are mostly dependent upon their families, an element of coercion can also manifest. Also, determining whether a child rationally consented to donate an organ to their parent, for example, becomes difficult when we factor in the emotional element of their relationship that can perhaps override their judgments about their own safety.

Another concern is the well-being of the savior sibling throughout their life, both physical and psychological. Whats to stop a parent from asking the savior sibling to be on standby for their entire lives for their siblings health, available to be tapped for tissues and organs at any point in their lives? This is the plot of Jodi Picoults My Sisters Keeper (also turned into a film of the same name starring Cameron Diaz), but it is an unlikely scenario in real life, ethics experts have said. The aforementioned organ donation rules can prevent such an exploitative situation from arising, they say, with governments around the world tasked with ensuring the consent of the donor remains at the forefront of organ donation.

The third issue with savior sibling therapy arises out of the process itself if a parent can select an embryo that perfectly matches their child, whats to stop them from selecting an embryo for intelligence, or athleticism? This wades into the territory of the production of designer babies, which is an ethical slippery slope that critics have said goes against the natural reproductive order. However, the bioethics study asserts that the connection between savior sibling therapy and the production of designer babies is less of a slippery slope and more of a reach, as the technology might be similar, but the utility of both poles apart the former is used to save childrens lives, while the latter is a superficial, hypothetical fantasy.

For now, the world of savior sibling therapy, and its perception, remains similar to when parents first selected an embryo to create a savior sibling in the U.S. in 2000. As appeared in a New York Times article at the time, It is the kind of talk heard with every scientific breakthrough, from the first heart transplant to the first cloned sheep. We talk like this because we are both exhilarated and terrified by what we can do, and we wonder, with each step, whether we have gone too far. But though society may ask, How could you? the only question patients and families ask is, How could we not? 20 years later, savior sibling therapy still centers the children that can be saved, while government stipulations around the world try to ensure the savior siblings are protected, cared for, and treated as human beings, like any other child.

While a few critics argue for a ban, the bioethics study sums up the dilemma, and perhaps a solution to this ethical debate given that a ban will be fatal for a section of the population, the onus of proof rests clearly with the prohibitionists who must demonstrate that these childrens deaths are less terrible than the consequences of allowing this particular use of PGD.

You have got to have a very powerful reason to resist the means by which a childs life can be saved.

Read more from the original source:
An Indian Baby 'Savior Sibling' Just Gave Her Brother Bone Marrow. But Is It Ethical? - The Swaddle

Recommendation and review posted by Bethany Smith

Cecelia Ahern, the author of P.S. I love you, once beautifully said: Moments are precious; sometimes they linger and other times theyre fleeting, and yet so much could be done in them; you could change a mind, you could save a life and you could even fall in love.

Helping save lives is what we decided to dedicate some of our lives to at Manchester Marrow.More specifically, we are the student-ran arm of the charity Anthony Nolan, which signs up students/young people (aged 16-30 years) to the stem cell register. This is required in finding matches for patients suffering from blood cancers and blood disorders who desperately need transplants. The more people we sign up for this register, the higher the chance of finding a blood stem cell or bone marrow match.

Anthony Nolan was initially founded by Shirley Nolan in 1974, realising the hardships associated with requiring an urgent bone marrow transplant. This was due to her three-year-old son suffering from a rare blood disorder known as Wiskott-Aldrich Syndrome. This inspired her to set up the worlds first register to match donors with people in desperate need. Today, there are over 800,000 people on Anthony Nolans UK register list, and each of these people could be a potential donor and save a life.

Although there are many resources at hand, without you, theres no cure! In Marrow, we have three important missions: raise awareness of Anthony Nolan and blood cancer within UK universities through our events, encourage every student to join stem cell register through our donor recruitment opportunities, and lastly, raise funds to help support this vital work.

As a student, in addition to signing up to the register, you have the amazing opportunity of volunteering for us and to save a life! One of our most outstanding achievements is signing up over 100,000 people to the Anthony Nolan register and raising over 92,000 in a year. Additionally, 1 in 4 people who go on to donate stem cells is recruited via Marrow!

Being a volunteer for us is no hard work. You could do many things, including spreading the word and talking to people about why they should sign up to the register. Furthermore, you need to inform them what the donation involves if they ever found a match, checking medical backgrounds for donor eligibility, assisting them with cheek swabs, and filling out an application form.

If youre interested in this opportunity, there will be several volunteer training sessions held throughout the year. Unfortunately, due to the current situation, all these events will be held online. We can assure you, however, that were doing our best to make the most of it.

To sign up to the register visit the Anthony Nolan website!

Make sure to follow Manchester Marrows social media accounts to keep updated with all the news and events:

Facebook: @ManchesterMarrow

Facebook: Manchester Marrow Volunteers Group

Instagram: @manchestermarrow

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Looking to save lives? Here's how - The Mancunion

Recommendation and review posted by Bethany Smith

DetailsCategory: DNA RNA and CellsPublished on Friday, 16 October 2020 14:20Hits: 378

First therapy recommended for full marketing authorization in the EU for eligible patients with confirmed diagnosis of late infantile or early juvenile MLD variants

One-time treatment with Libmeldy has been shown to preserve cognitive and motor function in most patients

Libmeldy is backed by data across 35 patients with follow-up of up to 8 years post-treatment, demonstrating the potential durability of HSC gene therapy

BOSTON, MA, USA and LONDON, UK I October 16, 2020 I Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending full, or standard, marketing authorization for Libmeldy (cryopreserved autologous CD34+ cells encoding the arylsulfatase-A, or ARSA, gene), an investigational gene therapy for the treatment of metachromatic leukodystrophy (MLD), characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline.

The CHMPs positive opinion will now be reviewed by theEuropean Commission(EC), which has the authority to grant marketing authorization for Libmeldy in theEuropean Union(EU). A final decision by the EC for Libmeldy is anticipated before the end of 2020. If approved, Libmeldy would be the first commercial therapy and first gene therapy for eligible patients with early-onset MLD.

MLD is a very rare, severe genetic condition caused by mutations in the ARSA gene which lead to neurological damage and developmental regression. In its most severe and common forms, young children rapidly lose the ability to walk, talk and interact with the world around them. A majority of these patients pass away in childhood, with palliative care often as their only option.

Todays positive CHMP opinion for marketing authorization of Libmeldy is a remarkable achievement that we share with the MLD community, as it brings us closer to delivering a one-time, potentially transformative therapy for eligible children suffering from this devastating disease, said Bobby Gaspar, M.D., Ph.D., chief executive officer, Orchard Therapeutics. Data from the Libmeldy clinical program have demonstrated the potential for long-term positive effects on cognitive development and maintenance of motor function, translating to individual preservation of motor milestones such as the ability to sit, stand and/or walk without support, as well as attainment of cognitive skills like social interactions and school attendance, at ages at which untreated patients show severe motor and cognitive impairments.

Libmeldy is designed as a one-time gene therapy, developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy, in which the patients own hematopoietic stem cells (HSCs) are selected, and functional copies of the ARSA gene are inserted into the genome of the HSCs using a lentiviral vector before these genetically modified cells are infused back into the patient. The ability of the gene-corrected HSCs to migrate across the blood-brain barrier into the brain, engraft, and express the functional enzyme has the potential to persistently correct the underlying genetic condition with a single treatment.

This is an important milestone toward making the availability of HSC gene therapy a reality for more patients, and it also is extremely rewarding for our multi-disciplinary team at SR-Tiget who has worked relentlessly along this 15-year journey to move the seminal proof of principle studies to the first in-human testing of this therapy, said SR-Tiget director Luigi Naldini, M.D, Ph.D. The robust and durable clinical benefits observed in early-onset MLD patients who received HSC gene therapy are compelling, especially when compared to the natural history of the disease. These results also further illustrate our view that the HSC gene therapy approach has the potential to deliver transformative effects in other storage diseases as well, especially when the cells are designed to overexpress the functional enzyme and provide an enhanced supply of it to the affected tissues.

As a parent, watching your child start down a seemingly normal developmental path only to suddenly and rapidly lose some or all of his or her abilities is heart-wrenching, and the agony is even more acute knowing no approved therapies currently exist for MLD, said Georgina Morton, Chair of ArchAngel MLD Trust. Todays decision to advance Libmeldy to the final EC approval stage represents a huge step forward for the parents of these young children and for all of us in the MLD community.

We are extremely appreciative of the EMAs expedited and thorough review of Libmeldys marketing authorization application, considering the severity of MLD coupled with the limited treatment options available today for young patients, said Anne Dupraz, chief regulatory officer, Orchard Therapeutics. The Agencys collaboration on this assessment is a testament to their broader public health commitment to ensure timely evaluation of new medicines for diseases where a pressing unmet need exists.

Data Supporting the Clinical Profile of Libmeldy

The positive CHMP opinion is supported by clinical studies of Libmeldy in both pre- and early- symptomatic, early-onset MLD patients. Early-onset MLD encompasses the disease variants traditionally referred to as late infantile (LI) and early juvenile (EJ).

Clinical efficacy was based on the integrated analysis of results from 29 patients with early-onset MLD who were all treated with Libmeldy prepared as a fresh (non-cryopreserved) formulation:

Clinical safety was evaluated in 35 patients with early-onset MLD:

Co-primary endpointsThe co-primary endpoints of the integrated efficacy analysis were Gross Motor Function Measure (GMFM) total score and ARSA activity, both evaluated at 2 years post-treatment. Results of this analysis indicate that a single-dose intravenous administration of Libmeldy is effective in modifying the disease course of early-onset MLD in most patients.

Pre-symptomatic LI and EJ patients treated with Libmeldy experienced significantly less deterioration in motor function at 2 years and 3 years post-treatment, as measured by GMFM total score, compared to age and disease subtype-matched untreated patients (p0.008). The mean difference between treated pre-symptomatic LI patients and age-matched untreated LI patients was 71.0% at year 2 and 79.8% at year 3. Similarly, the mean difference between treated pre-symptomatic EJ patients and age-matched untreated EJ patients was 52.4% at year 2 and 74.9% at year 3. Although not statistically significant, a clear difference in GMFM total score was also noted between treated early-symptomatic EJ patients and age-matched untreated EJ patients (28.7% at year 2; p=0.350 and 43.9% at year 3; p=0.054).

A statistically significant increase in ARSA activity in peripheral blood mononuclear cells was observed at 2 years post-treatment compared to pre-treatment in both pre-symptomatic patients (20.0-fold increase; p<0.001) and early-symptomatic patients (4.2-fold increase; p=0.004).

At the time of the integrated data analysis, all treated LI patients were alive with a follow-up post-treatment up to 7.5 years and 10 out of 13 treated EJ patients were alive with a follow-up post-treatment of up to 6.5 years. No treatment-related mortality has been reported in patients treated with Libmeldy.

Key secondary endpointsFor EJ patients who were early-symptomatic when treated with Libmeldy, meaningful effects on motor development were demonstrated when these patients were treated before entering the rapidly progressive phase of the disease (IQ85 and Gross Motor Function Classification (GMFC)1). By 4 years post-disease onset, an estimated 62.5% of treated, early-symptomatic EJ MLD patients survived and maintained locomotion and ability to sit without support compared with 26.3% of untreated early-symptomatic EJ MLD patients, representing a delay in disease progression following treatment with Libmeldy.

A secondary efficacy endpoint that measured cognitive and language abilities as quantified by Intelligence Quotient/Development Quotient (IQ/DQ) found:

Clinical safetySafety data indicate that Libmeldy was generally well-tolerated. The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies (AAA) reported in 5 out of 35 patients. Antibody titers in all 5 patients were generally low and no negative effects were observed in post-treatment ARSA activity in the peripheral blood or bone marrow cellular subpopulations, nor in the ARSA activity within the cerebrospinal fluid. Treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

About MLD and Investigational Libmeldy

Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease of the bodys metabolic system occurring in approximately one in every 100,000 live births. MLD is caused by a mutation in thearylsulfatase-A(ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. Currently, there are no approved treatments for MLD. In its late infantile form, mortality at 5 years from onset is estimated at 50% and 44% at 10 years for juvenile patients.1Libmeldy (autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced ex vivo using a lentiviral vector encoding the human arylsulfatase-A (ARSA) gene), formerly OTL-200, is being studied for the treatment of MLD in certain patients. Libmeldy was acquired from GSK inApril 2018and originated from a pioneering collaboration between GSK and the Hospital San Raffaele and Fondazione Telethon, acting through their jointSan Raffaele-Telethon Institute for Gene TherapyinMilan, initiated in 2010.

About Orchard

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

1 Mahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature.Journal of Child Neurology2010, DOI:http://doi.org/10.1177/0883073809341669

SOURCE: Orchard Therapeutics

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Orchard Therapeutics Receives Positive CHMP Opinion for Libmeldy for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD) | DNA RNA and...

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INTRODUCTION

Over the past decade, there have been great successes in assembling high-performance biological and electronic materials with thin and sophisticated architecture. For example, monolayered cell sheets have shown to reproduce physiological activities of original tissue and exhibit enhanced therapeutic efficacy than individual cells because of increased cell-cell interactions and the presence of an extracellular matrix (14). These cell sheets are being studied extensively to assemble in vitro disease models and treat wounded or defective tissues and organs. Separately, minimizing the thickness of wearable electronic devices enables conformal adhesion without an interfacial gap and, in turn, improves performance for sensing, diagnosis, and therapies (58). However, handling such delicate and thin materials for transport and assembly remains a grand challenge. External forces used for gripping, holding, and discharging such materials often deform, wrinkle, or damage materials (9). Such damage can be avoided by attaching thin materials to sacrificial polymeric supports including water-soluble or thermal release tapes (1012). However, these supports should be removed with chemical or long-lasting heat treatment following the placement of thin materials onto a target site, thus making them not reusable.

Recently, efforts have emerged to transport thin electronic materials by simulating the ability of cephalopods (e.g., octopus and squid) to capture and release their preys (1315). Cephalopods use many muscle-based suction cups, called suckers, on their arms to attain conformal adhesion to target preys in both wet and dried environments (16, 17). Bioelectrical signals control the rapid contraction and relaxation of the soft muscle and, in turn, change the internal pressure of the suckers. However, most material-handling systems that were devised to mimic the suction cups focus on recapitulating the anatomical structure but overlook the roles of the bioelectrical signal for control. Therefore, these strategies require mechanical force to be applied externally to attach and detach materials of interests. In addition, synthetic suction cups made with polydimethylsiloxane (PDMS) or polyurethane acrylates are more rigid than biological suction cups by two or three orders of magnitude (13, 15). Such rigid suction cups require higher external pressure for gripping than biological ones, thus increasing the possibility to damage thin and soft materials. Certain efforts were made to assemble a device that can hold and detach materials with heat by coating porous PDMS with thermally responsive poly(N-isopropyl acrylamide) (PNIPAAm) (14). However, the manipulation process was only possible while submerged in a water bath. In addition, it takes 30 min to hours for the device to move one material from one place to another.

To this end, we demonstrate a soft manipulator that can repeat the holding and unloading of thin and fragile materials within 10 s in response to an electrical signal. We hypothesized that a rapid thermo-responsive, microchanneled hydrogel layered with a microelectric heater would lift and release materials of interests without applying an external force due to temperature-induced internal pressure change in microchannels of the gel (Fig. 1). In addition, gels tailored to be as soft as biological suction cups would allow fast and notable changes in internal pressure in response to small temperature changes while minimizing the amount of force imparted onto the thin material to be transported. We examined this hypothesis by attaching a flexible electric heater, which converts electrical signals into heat, to a microchanneled PNIPAAm hydrogel. We examined the extent that the electrothermal signal controls the shrinkage and expansion of microchannels of the gel along with subsequent pressure change inside microchannels. The resulting soft manipulator was assessed for its ability to lift up and release thin materials onto target tissues promptly in response to the electrothermal signal. These thin materials include therapeutic stem cell sheets and ultrathin, wearable bioelectronic devices.

Schematic illustration of (A) the soft, electrothermally controlled manipulator and (B) the process to transport a thin material using the soft manipulator. (A) The soft manipulator consists of a supporter, flexible heater that can convert electrical current to heat, cyanoacrylate-based wet adhesive, and a thermo-responsive PNIPAAm hydrogel with aligned microchannels. (B) Process to transport materials of interests using the soft manipulator. First, the soft manipulator is lowered to let the gel contact a thin material such as a therapeutic cell sheet or an ultrathin film device. During this step, the heater is turned on to contract microchannels of the gel. Second, the heater is turned off to open microchannels of the gel and generate negative pressure in microchannels. As a consequence, the gel serves to hold, lift up, and transport the thin material. Third, the heater is turned on to close microchannels of the gel and, in turn, generate positive pressure in the microchannels. The positive pressure serves to release the thin material onto the target surface.

We prepared a hydrogel that undergoes a rapid volumetric change in response to a temperature change by introducing anisotropically aligned microchannels into the PNIPAAm gel. The microchanneled gel was assembled by placing the pregelled NIPAAm solution on top of a liquid nitrogen reservoir. Then, ice crystals nucleated from the bottom and grew to the top surface due to the temperature gradient (step 1 in Fig. 2A). Simultaneously, solutes, including NIPAAm monomer, cross-linker, and photo-initiator in the solution, were separated from the growing ice crystals because of the decreased solubility in ice crystals (step 2 in Fig. 2A). This continuous and directional segregation of the solutes formed a cryo-concentrated phase between growing ice crystals. Subsequent exposure of the frozen sample to ultraviolet (UV) lightactivated polymerization and cross-linking reaction fixed the anisotropically aligned PNIPAAm network (step 3 in Fig. 2A) (18, 19). The final washing process with the water removed ice crystals and created a PNIPAAm gel with continuously aligned microchannels (Fig. 2B). The resulting gel exhibited an average microchannel diameter of ~20 4 m and an average wall thickness of 0.2 m in the gel at room temperature (Fig. 2C). The porosity reached 95 1%.

(A) Schematic illustrating the fabrication process of the gel with anisotropically aligned microchannels. The gel is prepared by directional crystallization and subsequent polymerization. (B) Photograph of the resulting microchanneled hydrogel after swelling in water. (C) Microstructure of the gel: (C-1) scanning electron microscopy (SEM) micrograph of the top surface, (C-2) 3D imaging of the microchanneled hydrogel via microcomputed tomography (micro-CT), and (C-3) SEM micrograph of microchannels that connect the top and bottom of the gel. (D) ESR of gels at different temperatures. (E) Compressive elastic moduli of gels. Samples were compressed in parallel with microchannel direction (axial compression) and perpendicular to microchannel direction (radial compression). (F) Time-dependent volumetric changes of microchanneled gel on heating (F-1) and cooling (F-2). The samples were placed on 40 or 25C plate. The resulting volumetric change was recorded. (G) Effective diffusion coefficient of water in gels quantified by the reswelling plot (F-2). * represents the statistical significance of the difference of values between conditions indicated with line (*P < 0.01). Photo credit: Byoungsoo Kim, University of Illinois at Urbana-Champaign.

For comparison, randomly oriented water crystals were created in the PNIPAAm gel by placing the pregelled NIPAAm solution in a freezer at 25C and curing it under UV light. The resulting hydrogel showed a similar porosity to the PNIPAAm gel prepared by directional crystallization. However, the microchannels of varying diameters were oriented randomly (fig. S1). In addition, PNIPAAm gel free of microchannels was prepared by skipping the crystallization step.

We examined the equilibrium swelling ratios (ESRs) of the resulting gels. All samples showed the volumetric swelling change at around 32C, which corresponds to the lower critical solution temperature (LCST) of PNIPAAm (Fig. 2D). The difference in the ESR between 25 and 35C was dependent on the microchannel architecture of the gel. In particular, gels with anisotropically aligned microchannels showed a 2.7-fold higher swelling ratio than those with randomly oriented microchannels and a 1.4-fold higher swelling ratio than those free of microchannels. The elastic modulus of the gel with anisotropically aligned microchannels was dependent on the direction of microchannels (Fig. 2E). The elastic modulus measured by compressing the gel perpendicular to the microchannel was 2.4 kPa, which was twofold lower than that measured by compressing the gel in parallel with the microchannels. In contrast, the gel with randomly oriented microchannels and the gel free of microchannels showed the minimal dependency of the elastic modulus on the direction of compression.

Next, we examined the extent that the microchannel architecture of the gel modulates the volumetric swelling rate in response to temperature change. The gel without microchannels exhibited minimal volumetric change over 10 s when the temperature was increased from 25 to 40C. In contrast, the gel with anisotropically aligned microchannels reduced its volume by 60% within 10 s when temperature increased to 40C (Fig. 2F-1 and movie S1). This heat-triggered shrinkage is attributed to the decrease of the average cross-sectional diameter of microchannels from 20 to 9 m as examined with scanning electron microscope images (fig. S2). The microchannel alignment was maintained during the shrinkage. The gel with randomly oriented microchannels also shrank within 10 s when temperature increased to 40C (Fig. 2F-1). However, the degree of shrinkage was approximately 0.4, which was 20% lower than the gel with anisotropically aligned microchannels. The electron microscopic images showed lots of open voids as well as micropores collapsed incompletely (fig. S3). In contrast, the gel with aligned microchannels exhibited a more uniform decrease in the microchannel diameter and minimal macro-sized voids after heating (fig. S2). This result indicates that micropores of varying diameters and orientation limit heat-induced collapse, thus leading to the decreased volume shrinkage.

Cooling the gel from 40 to 25C resulted in gel expansion. The speed and degree of volumetric expansion were dependent on the microchannel architecture. The gel without microchannels did not recover its original volume even after 1 hour (Fig. 2F-2 and fig. S4). In contrast, both of the gels with microchannels restored their original volume within 10 s due to reswelling. The reswelling plot displayed in Fig. 2F-2 was used to quantify the effective water diffusion coefficient (Fig. 2G). We used the Higuchi equation derived under the steady-state approximation of Ficks law of diffusion as follows (20)Vt=V25(S/V40)(Dt/)1/2(1)where Vt is the volume of a gel at time t, D is an effective diffusion coefficient, and S is an effective surface area. V40 and V25 are the volume of a gel at 40C and 25C, respectively. We assumed that water diffusion occurred exclusively on the gel surface. Anisotropically microchanneled gels had a 75-fold higher water diffusion rate than the gel free of microchannels (Fig. 2G). In addition, the gel with anisotropically aligned microchannels showed a 10% higher water diffusion rate than that of the gel with randomly oriented microchannels.

Separately, a flexible electric (joule) heater was fabricated to be attached to the gel by photolithographic patterning of a copper/polyimide film (thickness, 9-m copper/12-m polyimide). The linewidth and spacing of the copper pattern was kept at 300 m to provide uniform heat across the gel disk (Fig. 3A). The heater was additionally coated with a layer of tin (thickness, ~1 m) to prevent oxidation of the copper at an increased temperature within a humid environment. The heater was then connected to an external power supply with a voltage range of 2 to 5 V (Fig. 3B). The activated temperature was examined using an infrared camera, showing that the heater reached the target temperature at 37C within 5 s after applying a voltage of 2 V (Fig. 3, A and B). After the power was turned off, the temperature was dropped immediately back to 25C. Such electrothermal heater was attached to the gel disk using a cyanoacrylate-based adhesive (21). The bilayered hydrogel-heater construct was finally attached to a three-dimensional (3D) printed supporter (Fig. 3C).

(A) Photograph (top) and a thermal image of the flexible heater captured using an infrared camera (bottom). (B) Temperature change over time at differently applied voltages. The temperature profiles of the heater were obtained using an infrared camera. (C) Structural configuration of the soft manipulator (left) and a photograph of the soft manipulator (right). (D and E) Top: Snapshots of the microchanneled gel in the soft manipulator when the heater was turned on (D) and off (E). Images on the second row represent optical microscopic images of the gel surface when the heater was turned on and off. When the heater was turned on, aligned microchannels of the gel pushed water out while being closed for 20 s (D). When the heater was switched off, the gel in the soft manipulator opened microchannels and pulled water back into microchannels within 20 s (E). Scale bar, 100 m. Photo credit: Byoungsoo Kim, University of Illinois at Urbana-Champaign.

With the resulting electrothermal soft manipulator, we examined the response of the gel disk to the electrical signal. The test was conducted outside water. Figure 3 (D and E) shows the side view of the gel disk and the microstructural changes of the gel surface during the electrically controlled heating and cooling cycle. Switching on the heater triggered shrinkage of microchannels within 10 to 20 s and simultaneously released a fraction of water from the gel (Fig. 3D and movie S2). With the power off, the gel expanded the microchannels and reabsorbed the water within a few seconds (Fig. 3E and movie S2). The shrinkage and expansion of microchannels could be repeated hundreds of times by turning the power on and off. No structural failure of the gel was observed during repeated operation. We further examined the heat transfer through the gel layer placed on the heater at a temperature of 40C (fig. S5A and movie S3). With the heater on, the temperature of the gel increased rapidly from the bottom (point 1 in fig. S5B) to a top (point 4 in fig. S5B) within 20 s. This result confirms heat propagation along the gel thickness direction. The gel temperature increased at a rate of 0.3C/mms, independent of the region of observation. Last, the temperature of the entire gel became equal to that of the heater within 30 s (fig. S5C).

The gel with randomly oriented microchannels also underwent shrinkage and expansion in response to the electrothermal signal. However, the area undergoing microchannel shrinkage and expansion was not as uniform as in the gel with anisotropically aligned microchannels (fig. S6). Therefore, the gel released water locally. The gel without microchannels showed a very slow release and limited absorption of water when the electric heater was on and off, respectively (fig. S7).

The shrinkage and expansion of anisotropically aligned microchannels allowed the gel to grip, lift, and release materials of interest (Fig. 4A and movies S4 and S5). The manipulator with a diameter of 25 mm was used in this study. The manipulation process was conducted as follows. First, we shrank the upper part of the microchannels of the hydrogel by activating the heater (stage 1 in Fig. 4A). During this process, the gel released a fraction of water, thus creating an empty pocket between the heater and residual water in the microchannels. The gel was then placed on a 4-inch-diameter silicon wafer, a model material that should be transported (stage 2 in Fig. 4A). Next, the heater was deactivated to expand the shrunken microchannels and move residual water upward [stage 3 (i) in Fig. 4A]. The subsequently formed vacant space between water within the microchannels and the silicon wafer decreased the pressure inside microchannels, thus making the gel adhere to the silicon substrate. Thus, the soft manipulator could lift the substrate [stage 3 (ii) in Fig. 4A]. Last, with the power on, microchannels adjacent to the heater shrank and pushed water out of the microchannel (stage 4 of Fig. 4A). The subsequent pressure increases inside the microchannels served to dislodge the silicon wafer quickly. This mechanism is distinct from artificial handling systems assembled with an inspiration from anatomy of the cephalopods suction cup. These handling systems, however, require external force to hold and release materials of interest. In contrast, the manipulation process performed by our soft manipulator resembles the neuromuscular actuation in which cephalopods grip and release materials of interests. Through control of electricity, the rapid electrothermal actuation of the gel enabled the manipulator to systematically lift up and release target materials without external forces.

(A) Snapshots showing the transport of a 4-inch-diameter silicon wafer using a soft manipulator (upper images). Schematic illustrating the shrinkage and expansion of microchannels and subsequent water movement in microchannels controlled by the electrothermal signal (bottom images). The operating power of the soft manipulator was 5 W. (B) The time-dependent variation of normal adhesion strength measured by the dynamic mechanical analyzer (DMA) during stages 2 and 3 in (A). An initial contact strength of 0.05 kPa was applied to the soft manipulator for this measurement. (C) Fluorescence images of water in microchannels of the gel. The image was obtained from a 3D z-stack confocal microscope before (top) and after adhesion (bottom) of the soft manipulator to a target surface. The heater was attached to the upper part of the gel. (D) Dependency of the adhesion strengths on the initial load. (E) Variation in the adhesion strength as a function of cycle number. (F) Adhesion strength of the soft manipulator measured with the various target substrates in water and air. An initial contact strength of 0.5 kPa was applied to the soft manipulator using DMA for this measurement. Photo credit: Byoungsoo Kim, University of Illinois at Urbana-Champaign.

The normal pressure development of the gel to the silicon surface was further measured, particularly during stages 2 and 3. This measurement was conducted by attaching the bilayered gel-heater construct to a dynamic mechanical analyzer (DMA) (Fig. 4B). First, the gel was preheated by the heater and brought into contact with a 4-inch silicon wafer (Approaching stage in Fig. 4B). Next, when the power was turned off to expand microchannels, the load was increased in the negative direction for 25 s (Gel expansion stage in Fig. 4B). This bilayered gel-heater construct was then slowly pulled upward at 0.1 mm/s by DMA to monitor the increase of the adhesion strength (Adhesion stage in Fig. 4B). The maximum adhesion strength reached 1.5 kPa. Once the power was turned on before the stress reached 1.5 kPa, the normal adhesion strength decreased quickly to 0 kPa within 5 s (Unloading stage in Fig. 4B).

Without temperature control, the manipulator does not exhibit adhesion. We further examined whether temperature-induced contraction and expansion of microchannels are essential to create adhesion. The soft manipulator preheated to 37C was placed on the silicon wafer immersed in water with controlled temperatures. Then, the heater of the soft manipulator was turned off. At temperatures below LCST of the gel layer (i.e., ~32C), the adhesion strength increased rapidly with decreasing temperatures (fig. S8). This result confirms that temperature of the heating layer in the manipulator controls the degree of expansion of the microchanneled gel layer and, in turn, regulates adhesion strength.

We propose that the electrothermally controlled adhesion of the gel to the silicon wafer results from the pressure difference (P) between two ends of microchannels. We introduced the mixture of rhodamine B and water into microchannels of the gel and monitored the vertical movement of water through the individual microchannel during stage 3 (i) in Fig. 4A. According to the side view of the gel captured with confocal microscopy, the microchanneled gel disk was fully filled with water (Fig. 4C, top). Heating and the subsequent cooling process resulted in the space in the lower part of the microchannel adjacent to the silicon substrate by moving residual water upward in the microchannels (Fig. 4C, bottom). This image is similar to the scheme that represents stage 3 in Fig. 4A. The average height of space in the microchannel was approximately 50 m. The pressure difference of a single microchannel in the gel was quantified with a height of the empty part in the microchannel as followsP=wg(hihf)(2)where w is the density of water, g is the gravitational acceleration, and hi and hf are the height of the space in microchannels when the power was turned on and off, respectively. According to the calculation, each microchannel in the gel produced 0.5 Pa of negative pressure after the cooling process.

The adhesion strength of the gel to the silicon wafer was dependent on the initial load applied to the soft manipulator (Fig. 4D). The maximum adhesion strength reached 65 kPa with the initial pressure of 5.0 kPa. The maximum adhesion strength reached 65 kPa with the initial pressure of 5.0 kPa. To underlie the mechanism, we examined the normal pressure development that varies with the initial contact pressure using a DMA. As shown in fig. S9A, the heated soft manipulator was placed on the target silicon wafer. As soon as the heater was turned off, the gel layer expanded and pushed the silicon wafer more strongly. As a consequence, the normal pressure developed in the opposite direction. The normal pressure increased with the initial contact pressure (fig. S9B). Increasing the initial contact pressure enlarged the effective suction area of the soft manipulator and also augmented the normal pressure.

We also examined the effect of elastic modulus of target materials on the adhesion strength. We prepared alginate hydrogels with elastic moduli of 22.5 and 69.8 kPa as target materials for transport (fig. S10A). As confirmed with the pressure development profiles, with a given initial contact pressure of 0.25 kPa, the soft manipulator exhibited a similar magnitude of the adhesion strength to the alginate gels as well as the silicon wafer with a much higher elastic modulus of 140 to 180 GPa. This result suggests that it is not necessary to vary the initial contact pressure with the target material stiffness (fig. S10B). The adhesion strength was not reduced during the repeated cycles of closure and opening of microchannels (Fig. 4E). No chemical contamination or residue was observed on the silicon wafer after the process (fig. S11). The soft manipulator could transport plastic and glass materials by exerting a similar magnitude of the adhesion strength regardless of material hydrophobicity (Fig. 4F). The soft manipulator functioned to transport materials immersed in aqueous media and those in the air.

Last, we examined the capability of the soft manipulator to lift up, transport, and release ultrathin and delicate materials, such as living cell sheets and ultrathin thin film devices. We prepared a single-layered mouse skeletal myoblast cell sheet on a culture dish. In general, monolayered cell sheets were easily damaged or crumpled when picking up the sheet from the cell culture dish with forceps (Fig. 5A and movie S6). By switching the heater of the soft manipulator on and off, it was possible to lift the myoblast cell sheet and transport them to the new target sites. First, we transferred the cell sheet to a glass dish using the soft manipulator (Fig. 5B). Then, we examined whether the soft manipulator damages the sheet during transplantation. Off-axis deformation and viability of the cell sheet before and after delivering process were measured using the spatial light interference microscopy (SLIM) and the live-dead assay kit, respectively. According to SLIM observation and live-dead assay results, there was no substantial wrinkling nor loss of viability of cells that formed the cell sheet during this transport process (Fig. 5C and fig. S12). This simple transportation process allowed us to fabricate a 3D tissue by stacking multiple myoblast sheets using the soft manipulator (Fig. 5D). The resulting three-layered myoblast tissue showed a dense construct with three different layers.

(A) Snapshots of a process to pick up a skeletal myoblast sheet with forceps. The cell sheet was deformed when picking up the sheet using forceps (right). The cell sheet was stained with methylene blue for visualization. (B) Snapshot of a process to transport the skeletal myoblast sheet onto a glass surface using the soft manipulator. (C) Spatial light interference microscopy (SLIM) images of the cell sheet before (left) and after (right) the transfer, showing off-axis diffraction of the cell sheet. (D) Fluorescence image of a multilayered cell sheet consisting of three different myoblast sheets. The multilayered sheet was prepared by stacking cell sheets using the soft manipulator. (E) Snapshots of a process to transport a skeletal myoblast sheet onto a muscle tissue. It took 30 s for the entire transfer process. (F) Photographs of a rat eye before and after transplantation of a stem cell sheet. The cell sheet transplanted to the corneal epithelium of a rat eye using the soft manipulator. It took 30 s for the entire transfer process. (G) Histological examination of the rat eye before (left) and after (right) a stem cell sheet transfer. Hematoxylin and eosin staining revealed that the stem cell sheet was able to be successfully transplanted onto the anterior corneal surface without substantial interface space generation. Photo credit: Byoungsoo Kim, University of Illinois at Urbana-Champaign.

The soft manipulator allowed us to pick up various types of cell sheets and deliver them rapidly to any target surfaces. As a demonstration, we delivered the myoblast cell sheet to an ex vivo muscle tissue without any structural breakages (Fig. 5E and movie S7). The entire transport process could be completed within 30 s. In contrast, the soft manipulator assembled using a gel with randomly oriented micropores could not uniformly deliver the cell sheet due to the nonuniform micropore shrinkage (fig. S13). We also used the soft manipulator as a device to support atraumatic transplantation of a stem cell sheet to the anterior surface of the cornea. Similar to the myoblast cell sheet, mesenchymal stem cell sheets on a donor substrate could be easily transferred to the corneal epithelium of a rat eye (Fig. 5F). We confirmed the stable attachment of the stem cell sheet to the anterior surface of the cornea, in the position of the corneal epithelium of the rat eye by histological observation (Fig. 5G). A method to atraumatically transplant ex vivo generated stem cell sheets could simplify surgical technique and expand access to corneal epithelial stem cell transplants and it could have useful application in the treatment of corneal epithelial injuries, persistent epithelial defects, limbal stem cell deficiencies, nonhealing corneal ulcers, and blast injuries (22, 23).

In addition, the soft manipulator was used to transport an ultrathin electrophysiological (EP) sensor (thickness, ~1 m) without causing wrinkling. We fabricated the EP sensor that consists of reference, ground, and measurement electrodes allowing high-quality recording of electrocardiogram (ECG) signals (Fig. 6A) (24, 25). Generally, such ultrathin film devices were easily crumpled when picking up from a donor substrate, which typically requires the use of a temporary handling support (fig. S14 and movie S8). By using the soft manipulator, it was possible to controllably transfer the EP sensor from the donor substrate to the surface of the pig heart within a minute (Fig. 6B and movie S9). No substantial wrinkles were observed after completing the transport (Fig. 6C). A waveform generator was used to apply a preprogrammed ECG signals across the pig heart using an Ag/AgCl electrode. The resulting ECG signals captured from the EP sensor were nearly identical to those generated from the waveform generator (Fig. 6D and fig. S15). The Pearsons correlation coefficient of the signals was 0.98.

(A) Device configuration of the ultrathin EP sensor (t = 1 m) tailored for the measurement of ECG signals. (B) Snapshot of a process to transport the device to the surface of the pig heart. It took 30 s to capture and deliver the device onto the pig heart. (C) Photograph of the device transplanted to the pig heart using the soft manipulator. (D) Representative ECG signals measured using the transplanted device. Photo credit: Byoungsoo Kim, University of Illinois at Urbana-Champaign.

Together, this study demonstrates that the soft manipulator assembled by integrating a rapid thermal-responsive microchanneled gel and an electrothermal heater can transport ultrathin biological and electronic materials quickly and safely. The resulting soft manipulator could be switched on and off with electricity to lift and release thin and delicate materials within tens of seconds. This rapid handling could be attained with the electrothermally controlled change in the adhesion force between the soft manipulator and target materials. Such an actuation mechanism is very similar to the muscular action of cephalopod suction cups. Therefore, this soft manipulator is distinct from previous suction cupmimicking platforms that need external force for detachment of materials. In addition, the soft manipulator could move thin materials of interest in both wet and dry conditions. Using this unique functionality, we could assemble multilayered cell sheets and place an ultrathin biosensor to the target tissue without impairing its function.

We envisage that further modification of this soft manipulator with an electronic sensor would allow robots to transport ultrathin materials autonomously. For instance, the resulting smart soft manipulator would be able to monitor the degree of deformation of transporting materials during contact and, in turn, adjust the suction force to a level at which materials retain their structural integrity and functionality. By doing so, the soft manipulator would improve its performance from the standpoint of safety and accuracy of material handling and assembly. We believe that the present design concept may be widely used as a new soft handling tool for the fabrication of ultrathin film devices, tissue engineering, and transplant surgery.

This study demonstrated an electrically controllable soft machinery useful to transport ultrathin, delicate objects, including therapeutic cell sheets and thin, wearable biosensing devices. This system, named as the electrothermal soft manipulator, consisted of a flexible heater attached with a rapid thermo-responsive PNIPAAm hydrogel disk with controlled microchannel architecture and tissue-like softness. Compared with hydrogels free of microchannels or those with randomly oriented microchannels, the anisotropically aligned PNIPAAm hydrogel could shrink and expand in response to the electrically induced heat much faster, on the order of seconds. Such a fast-volumetric change of the microchannels on the surface of an object could produce and remove pressure-induced adhesion repeatedly. This controlled actuation mechanism is similar to the activity of cephalopod suction cups that hold and release objects of interest using bioelectric signals. As a consequence, the soft manipulator could move thin biological and bioelectronic devices quickly in both wet and dry conditions without causing wrinkling or damage of the thin materials. Such an electrothermally controlled soft manipulator would be useful to various applications that require the sophisticated manipulation of fragile and delicate biological tissues and bioelectronic devices.

NIPAAm (1.25 g) and N,N-methylenebisacrylamide {12.5 mg [0.01 weight % (wt %) of NIPAAm]} were dissolved in distilled water (8.75 ml) for 1 day at 25C to ensure the complete dissolution. Then, 25 mg (0.5 wt % of NIPAAm) of radical photo-initiator (Irgacure 2959) was added into the obtained solution and stirred until all the solids completely dissolved. The resulting pregelled NIPAAm solution was poured onto a Si-wafer substrate (4 inches, 550 m thick) with silicone mold (50 mm by 50 mm by 1 mm or 20 mm by 20 mm by 10 mm). Then, the Si-wafer substrate was put on a liquid nitrogen reservoir for the directional crystallization of the pregelled NIPAAm solution. The distance between the bottom surface of the Si-wafer and the top surface of liquid nitrogen was 1 cm. After complete crystallization of the pregelled NIPAAm solution, the samples were irradiated with a UV lamp ( = 365 nm) for 6 hours at a 25C freezer for the radical cryo-polymerization. The as-prepared poly-NIPAAm gel (PNIPAAm) was then washed with fresh water three times to remove the ice crystals.

For comparison, PNIPAAm gel with randomly oriented microchannels was prepared by placing the pregelled NIPAAm solution in a freezer at 25C for random crystallization. Then, the resultant samples were cryo-polymerized and washed at the same condition described above. PNIPAAm gel free of microchannels was prepared by skipping the crystallization and subsequently irradiated with a UV lamp for 1 hour at 4C. All hydrogel samples were soaked in 250-ml distilled water at 25C, which was repeatedly replaced for 1 day to remove unreacted impurities before using them.

The morphology of microchanneled PNIPAAm gels was examined using an environmental scanning electron microscope (ESEM; Quanta FEG 450, FEI) and microcomputed tomography (micro-CT, MicroXCT-200, Xradia Inc.). For cross-sectional analysis, the samples were immersed in liquid nitrogen for 30 min and immediately cryo-fractured. One hundred points from 10 different ESEM images were taken to determine the average pore size. The porosity of gels was determined by the gravimetric method. The pore volume of gels was divided by the total volume of gels as followsPorosity(%)={(WswollenWdry)/w}/{(WswollenWdry)/w+(Wdry/PNIPAAm)}(3)where Wswollen and Wdry are the weights of swollen and dry gels, respectively; w is the water density; and PNIPAAm is the NIPAAm density (1.1 g/cm3).

For ESR measurement, we measured the weight of PNIPAAm gels at different temperatures (4 to 40C) with 4C increments. The ESR was defined using the following equationESR(%)={(WsWd)/Wd}100(4)

The hydrogel samples were equilibrated at each temperature for 12 hours and weighted (Ws) after removing excess water. The dry weight of the samples (Wd) was measured after lyophilization. Five samples of each PNIPAAm gel were averaged.

For dynamic deformation analysis of hydrogels in response to temperature change, hydrogel samples immersed in 25C were trimmed into a cylinder shape (d = 25 mm, t = 1 mm) and placed on a copper plate (t = 1 mm). Then, the plate was put onto a heated Peltier stage (40C) to investigate the deswelling kinetics of samples. For reswelling kinetics, deswelled samples were transferred to a cooled Peltier stage (25C). We monitored the volume change in response to temperature using an optical microscope that connected with the Peltier device (TP104SC-mK2000A, Instec). All optical images were analyzed using ImageJ software.

The compressive modulus of hydrogels was measured on an electronic universal testing machine (Instron 5943, Instron) equipped with a water bath. Samples were cut into a square shape (10 mm by 10 mm by 10 mm). All mechanical tests were conducted in a water bath (25C). There were five replicates for all mechanical tests.

The heater was fabricated on a copper/polyimide film (t = 9 m/12 m, Pyralux AC091200EV, Dupont). A standard photolithographic patterning with a dry film photoresist (Riston MM540, Dupont) followed by the wet etching method (CE-100, Transene Inc.) defined the copper layer into a joule heating element. The copper traces were coated with 1-m layer of tin (Sn) (421 Liquid Tin, MG Chemicals) to protect the copper from oxidation in elevated temperatures within a humid environment. The resulting heater was then connected to an external power supply, where a voltage range of 2 to 5 V and its thermal characterizations over time were recorded using an infrared camera (E40, FLIR Systems).

The cyanoacrylate-based adhesive was spread on top of the flexible heating array (21). Immediately after, the hydrogel was trimmed into a cylinder shape (d = 25 mm, t = 1 mm) and pressed onto the substrate. The bonding occurs within 30 s. The resulting gel/heater was attached to a 3D printed supporter using double-sided tape (VHB, 3M). Then, the soft manipulator was connected to an electrical power supply.

For dynamic deformation analysis of the soft manipulator in response to activation of a heater, a monochrome camera (DS-Qi2, Nikon) was attached to an optical microscope (Eclipse LV100, Nikon) for top-view analysis of the gel in the soft manipulator. A digital camera with an optical zoom macro lens (Canon, MP-E 65 mm) was used for the side view analysis of the soft manipulator. Gels in the soft manipulator were incubated with colored water (Green, McCormick) for visualization of water.

Adhesion tests were performed with a DMA (ESM303, Mark-10). The soft manipulator was mounted on a load cell of the DMA (M5-5 or M5-200, Mark-10), and the vertical approach and retraction speeds of the soft manipulator were 0.1 mm/s. Force-displacement profiles with time were measured at room temperature.

To examine the capability of the soft manipulator to handling materials with different elastic moduli, alginate hydrogels with elastic moduli of 23 and 70 kPa were used in this study. Pregelled alginate solution was prepared by mixing 2 wt % alginate solution in MES buffer (pH 6.5) with sulfonated N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. Then, the pregelled alginate solution was cross-linked by adding adipic acid dihydrazide (AAD). The elastic modulus of the alginate gels was controlled by varying the molar ratio between AAD and uronic acids of alginate (MAAD).

Cross-sectional fluorescence images were obtained from 3D z-stack confocal images (LSM 880, Carl Zeiss). We used Rhodamine B mixed with water for tracking of water inside the soft manipulator before and after the attachment process.

To investigate surface contamination of the soft manipulator, we performed adhesion tests to silicon wafers using either the soft manipulator or a commercial medical grade tape (Transpore, 3M). After detachment of the samples, the resulting wafer was incubated with a dye (Rhodamine B) for 30 min. All samples were washed with distilled water three times in total. Then, we dried the wafer surface using N2 gas and subsequently observed the wafer surfaces using fluorescent optical microscopy.

C2C12 cells (mouse skeletal myoblast cell line, CRL1772) and D1 cells (bone marrowderived mesenchymal stem cell line, CRL12424) were obtained from the American Type Culture Collection (ATCC). C2C12 or D1 cells were plated on temperature-responsive PNIPAAm-grafted culture dishes (d = 35 mm, UpCell, Thermo Fisher Scientific) with seeding density of 5 105 cells. The cells were then cultivated for 3 days according to the guidelines of ATCC. To harvest sheets, confluent cells were rinsed twice with warmed Dulbeccos phosphate-buffered saline (DPBS). Then, the monolayers were detached from the culture dish by lowering the incubation temperature from 37 to 20C.

The viability of cell sheets was examined using the LIVE/DEAD Viability/Cytotoxicity Assay Kit for mammalian cells (Invitrogen) according to the manufacturers instructions. The cultured cells or transferred cells were gently washed three times with DPBS. Calcein acetoxymethyl (AM) and ethidium homodimer-1 (EthD-1) were diluted together in DPBS. Diluted calcein AM and EthD-1 solution (1 ml) was added to cultured cells and kept for 45 min at room temperature. The live cells were stained with calcein AM, and dead cells were stained with EthD-1. After staining, cells were gently washed with 1 DPBS for three times and imaged with a fluorescence microscope (LSM-880, Carl Zeiss). Off-axis deformation of the cell sheets before and after the delivery process was quantified using SLIM. The optical system was assembled by attaching a SLIM module (CellVista SLIM Pro, Phi Optics) to the output port of an existing inverted phase-contrast microscope (26).

C2C12 cells were cultured onto a temperature-responsive culture dish to produce cell sheets as described above. After incubation, confluent cells were stained with Cell Tracker Orange CMRA (Invitrogen) or calcein AM (Invitrogen). Then, cell sheets were detached from the culture dish by lowering the incubation temperature from 37 to 20C. The detached cell sheets were captured and transferred using the soft manipulator with electrical heater control. A multilayered cell sheet was fabricated by repeating the transfer procedure. The resulting multilayered tissue structure was imaged using a fluorescence microscope (LSM-880, Carl Zeiss).

Long-Evans/BluGill rats were used in this study. All experimental protocols were in compliance with the National Institutes of Health Public Health Service Policy on Humane Care and Use of Laboratory Animals and were approved by the University of Illinois at Urbana-Champaign (UIUC) Institutional Animal Care and Use Committee. For fixation of the cornea, the perfusion needle was inserted into the left ventricle of the heart. A cut was made within the right atrium to allow blood evacuation. Saline was injected at a rate of 300 ml/min to clear the blood from the rat, followed by injection of paraformaldehyde (PFA) at 300 ml/min. The perfusion was confirmed by checking PFA dripping from the nose of the rate, stiffening of the extremities and the liver, and contractures of the musculature. After completing the perfusion, the stem cell sheet was placed on the rats cornea using the soft manipulator. The other rat eye was used as a control. Enucleation was then performed using microscissors.

Enucleation was followed by placement of the eyeball on dry ice then into a mold. The mold was subsequently filled with an optimal cutting temperature (OCT) compoundembedding medium to ensure OCT. Cryosectioning at 40-m slices was performed using a cryostat. Slices were then fixed using 4% PFA because the eyeball was fixed but not the stem cell sheet. The sample was washed three times in tris-buffered saline (TBS) for 5 min. The section was stained with hematoxylin and eosin staining, followed by dehydration in citrasol for 5 min. The stained tissue section was imaged using Axio Zoom.V16.

The fabrication of the EP sensor began by spin-coating a layer of poly(methyl methacrylate) (PMMA; ~1 m thick) on a glass substrate, followed by thermal annealing at 180C for 1 min. A subsequent layer of polyimide (~1 m thick) was coated and cured in a vacuum oven at 250C for 1 hour. Thin films of Cr and Au (t = 5 nm/150 nm thick) were deposited by using an electron beam evaporation. Photolithographic patterning using a negative-type photoresist (Riston MM540, DuPont) followed by wet etching with Au and Cr etchants (Transene) defined the joule-heating element. The resulting structure was submerged in acetone to dissolve the bottom PMMA layer. An anisotropic conductive film (ACF; HST-9805-210, Elform) was bonded to the terminals and was connected to an external data acquisition system. The measurement of ECG signals began by attaching two commercial conducting electrodes (30 mm by 24 mm, H124SG, Kendall) diagonally across the pig heart. The electrodes were then connected to an arbitrary waveform generator (3390, Keithley) to apply a preprogrammed cardiac waveform (1-Hz frequency, 50-mV amplitude). The EP sensor was transferred onto the surface of the pig heart with the soft manipulator. The sensor was connected to an external preamplifier (Octal Bio Amp, ADInstruments) and data acquisition unit (PowerLab 16/35, ADInstruments), where the captured ECG signal was digitally filtered with a band-pass filter at the bandwidth of 0.5 to 100 Hz.

Acknowledgments: Funding: This work was supported by the National Science Foundation (STC-EBICS grant nos. CBET-0939511 and CBET-1932192), the National Institutes of Health (1R21 HL109192), the Department of Defense Vision Research Program under Award (W81XWH-17-1-022), and the Jump ARCHES endowment through the Health Care Engineering Systems Center at University of Illinois at Urbana-Champaign and partly by Korea Institute of Science and Technology-Europe. C.H.L. is funded by the NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB: 1R21EB026099-01A1). E.E.H. acknowledges the financial support from the University of Illinois Beckman Institute Graduate Fellowship. H.C. and N.M. gratefully acknowledge funding support from the National Science Foundation under award no. 1554249 and the International Institute for Carbon Neutral Energy Research (WPI-I2CNER), sponsored by the Japanese Ministry of Education, Culture, Sports, Science and Technology. V.K.A. acknowledges financial support from National Institutes of Health, National Eye Institute K08 EY024339 and R01EY029409; Department of Defense, Congressionally Directed Medical Research Program, Vision Research Program W81XWH-17-1-0122 (V.K.A. and H.K.); Veterans Affairs Office of Research and Development I01BX004080; Unrestricted Grant from Research to Prevent Blindness, New York; and National Institutes of Health, National Eye Institute P30 EY001792. Author contributions: B.S.K. and H.K. designed this project and wrote the manuscript. M.K.K., Y.P., and C.H.L. developed the flexible heater and performed the electrophysiology recordings. Y.C. and S.G.I. supported the cell sheet preparation. E.E.H. and M.U.G. performed and analyzed animal experiments. H.C. and N.M. helped to investigate electrothermal actuation of the gel. K.M.S. and L.B.S. supported and advised on animal experiments. V.K.A., K.K., and K.-N.S. advised on the tissue transplantation. C.H. and G.P. performed SLIM observation of the cell sheet, W.C.B. and S.Y. performed adhesion tests, B.S.K. performed all other experiments. J.L., C.H.L., and H.K. supervised the project. All authors discussed the results and contributed to the final version of the manuscript. Competing interests: H.K., B.S.K., C.H.L., J.L., and M.K.K. are inventors on a provisional patent application related to this work filed by the University of Illinois at Urbana-Champaign, Purdue University, and Chung Ang University (filed on 31 August 2020; no. 63/072,634). The authors declare no other competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Fate TherapeuticsandCelyadsnatural killer (NK) cell biology-focused cell therapies could overcome cell persistence challenges and consequent efficacy concerns with redosing strategies, experts said.

One of Fate Therapeutics lead products, FT596, is an allogeneic, multitargeted, chimeric antigen receptor (CAR) NK cell product. Celyads autologous CYAD-01 and CYAD-02 and allogeneic CYAD-101 are CAR T cell products using NK cell specificity to target T-cells. One analyst considered the potential to redose allogeneic products as a key item to consider while assessing clinical potential. While clinical data establishing the additive efficacy advantages of giving multiple doses is still preliminary, redosing allogeneic products could increase their expansion and persistence, experts said. Autologous therapies carry source constraints, so the ability to manufacture and administer allogeneic therapies is an advantage, they said.

While past NK cell therapy data has been mixed, experts saw potential in CAR NKs like FT596 or CAR T-cell products engineered to express NKG2D like CYAD-101, given the advancements in cell production.

Phase I FT596 results in B-cell lymphomas/ CLL are expected at either the American Society of Hematology (ASH) meeting in December or an investor meeting in early 2021, as per a second analyst report. Phase I data for CYAD-01 and CYAD-02 in relapsed/refractory (r/r) acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are expected by YE20, as per the companys August corporate presentation. Celyads allogeneic CYAD-101 is being tested in a Phase I alloSHRINK trial (NCT03692429) in metastatic colorectal cancer (CRC), which has a primary completion date of November 2020.

FT596s sales are expected to reach $136m in 2026, according to a GlobalData Consensus forecast. Celyad did not respond to a request for comment.

Increasing the persistence of cell therapies once they are infused into a patient has been a challenge, especially with NK cell-based therapies, experts said. The issue of persistence and consequent efficacy is significant because the potential efficacy with Celyad and Fate Therapeutics platforms remains largely unknown, they added.

Because the immune system can recognise foreign cells, cell products would not last for more than a few weeks, said Dr Marco Davila, medical oncologist, in the Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida. With CAR T-cell therapies, the expansion and persistence of CAR cells are said to correlate with the durability of response, said Dr David Sallman, assistant member, Department of Malignant Hematology, Moffitt Cancer Center.

Strategies involving multiple doses of cell therapies could maximise the total dose, improve duration, and increase efficacy magnitude with both autologous and allogeneic cell therapies, said Dr Tara Lin, associate professor of medicine, University of Kansas Medical Center, Kansas City. Multiple infusions of therapy could also potentially lead to complete remission, said Sallman. In Fate Therapeutics Phase I FT500 (NCT03841110) study, patients had been given up to six doses of the therapy, which was not found to be toxic, according to Fate Therapeutics CEO Scott Wolchko. Redosing has the potential to offer multiple infusions as maintenance therapy, said Dr Jeffrey Miller, professor of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis.

The persistence of allogeneic therapies is not well understood, and it is unknown how long cells need to persist to be effective or whether persisting cells confer durability of response, said Wolchko. Giving multiple doses is one way to overcome the lack of persistence if it is an important factor for efficacy, he said. In a 4Q19 call, the FDA said it was allowing the dose to be repeated on a patient-by-patient basis, Wolchko said. In the alloSHRINK study, CYAD-101 is administered three times with a two-week interval between each administration in metastatic CRC, as per ClinicalTrials.gov.

However, even if the engineered cells do not persist in the body, the response rate and ability to eradicate the disease should not be limited, said Davila. With a limited lifespan, allogeneic cell therapies would dissipate as the patients immune system recovers, said Dan Kaufman. With the incorporation of interleukin (IL)-12 or IL-15 into the cell product, the cell therapy could persist without exogenous cytokines, said Kaufman. The FT596 construct contains an IL-15 fusion protein.

Experts cited the data from a Phase I / II (NCT03056339) investigator-led effort at MD Anderson Cancer Center using cord blood-derived anti-CD19 CAR NK cells as an example of an effective CAR NK therapy. The study by Rezvani and colleagues showed a persistence challenge did not seem to hamper the response, because once a critical threshold for cell expansion is crossed, the activity can be mediated, Davila said. Eleven r/r patients with CD19-positive cancers, such as non-Hodgkins lymphoma or CLL, were treated with a single infusion; eight had a response, including seven with a complete remission (Rezvani et al. [2020] N Engl J Med, 382, pp. 545553). Even if the cells do not persist, they expand to sufficient levels to eradicate the disease before they are lost, Davila added.

In the Phase I THINK(NCT03018405) CYAD-01 data, decreased bone marrow blasts were observed in eight patients, including five objective responses and one stable disease for three or more months, as per the company presentation. Responding patients did have blast clearances, but some of the remissions were short-lived and the cells did not persist in the system, said Sallman. However, the short hairpin (sh) ribonucleic acid (RNA) technology employed CYAD-02, which could increase persistence and expansion, said Sallman (Fontaine et al., [2019]Blood, 134[Suppl 1], p. 3931). ShRNA technology allows T cell engineering without the need for gene editing to inhibit alloreactivity and increase persistence, according to Celyad.

Ongoing research on improving preconditioning regimens by combining additional drugs could also help with the persistence of allogeneic products, said Davila. It is not known whether every dose needs a conditioning regimen, but since conditioning regimens can suppress a patients immune system for several months, it may not be necessary before every therapy infusion, he added.

Patients will not have to receive a preconditioning regimen before every cell infusion, said Wolchko, adding redosing FT500 was found to be safe. Celyads protocol does not specify the preconditioning strategy for redosing. No predictive biomarkers are available to explain why some patients respond well and others do not, said Sallman, adding it is critical to identify potential responders. Nonetheless, there is no way to predict clinical efficacy based only on preclinical data, so data is still needed, said Miller.

The economic advantage to developing off-the-shelf therapies has driven interest in NK-cell based platforms, said Miller and Davila. If quick treatment is needed, then an allogeneic NK cell therapy would be better than an autologous therapy, which may take up to six weeks to manufacture, said Sallman. While the results with autologous CAR T-cell therapies have been significant, their scale-up and costs are challenging, said Kaufman. Related Report

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The ability to use induced pluripotent stem cell (iPSCs) or cord blood cells as a source would help scale up the cell manufacture and allow effective results, said Kaufman. iPSCs provide advancement in expansion protocols, which can provide multiple doses, Miller added. Fate Therapeutics has an iPSC-derived NK cell franchise. Also, since T cell therapies require donor apheresis to collect cells in a process lasting four to five hours, it is not feasible to keep going back to the same donor, said Miller.

Moreover, newer platforms are expected to improve on past NK cell therapy trials, specifically those showing mixed efficacy. Past studies had feasibility limitations in getting the required number of cells, said Miller. Those small studies were conducted at a time when cell isolation and production systems were not as advanced as they are now, said Davila.

Manasi Vaidya is a Senior Reporter for Clinical Trials Arena parent company GlobalDatas investigative journalism team. A version of this article originally appeared on the Insights module of GlobalDatas Pharmaceutical Intelligence Center. To access more articles like this, visit GlobalData.

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