The Harvard Club of Boston honored seven women at its 2020 Bostons Most Influential Women Gala on Feb. 12, selecting each of the powerhouse recipients for outstanding achievement, influence, and leadership in their field.

The gala honored Drew Faust, president emerita and Arthur Kingsley Porter University Professor at Harvard; Annapurna Poduri, director of the epilepsy genetics program and Poduri Lab at Boston Childrens Hospital and associate professor of neurology at Harvard Medical School; Laurie H. Glimcher, president and CEO of the Dana-Farber Cancer Institute, director of Dana-Farber/Harvard Cancer Center, and Richard and Susan Smith Professor of Medicine at Harvard Medical School; Elizabeth L. Hailer, executive director of The Commonwealth Institute, a non-profit that promotes the advancement of female business leaders; Geri Denterlein, founder and CEO of public relations firm Denterlein; and Katey Stone, head coach of the Harvard womens ice hockey team.

In addition, the Harvard Club honored Sheena Collier with the Rising Star Award. Collier is the founder and CEO of The Collier Connection, which focuses on networking and resource building with the citys Black community. In addition, Collier works as a senior economic opportunity adviser for the Greater Boston Chamber of Commerce.

The gala also featured a musical guest, 17-year-old Lynn native Amanda Mena, who performed on Americas Got Talent in 2018.

Read the rest here:
The Harvard Club hosts the 2020 Bostons Most Influential Women Gala - The Boston Globe

Recommendation and review posted by Bethany Smith

David E. Wildts contributions to global conservation efforts will be felt for generations, his colleagues said in the wake of his passing.

Wildt, who died from cancer on Jan. 15 at the age of 69, was director of the Smithsonian Conservation Biology Institutes Center for Species Survival in Front Royal before retiring in December 2018.

He was not only a brilliant man and a diplomat, he was one of those special people who makes other people feel special, said Kelley Snodgrass, executive director of the Fossil Rim Wildlife Center in Texas.

Heck of a guy, Snodgrass said of Wildt in a Thursday phone interview. He could go from speaking about single nucleotide polymorphisms to tractors and his favorite chainsaw.

Wildts ability to get results from a diverse group of people is one of the things Snodgrass said hell remember most about his colleague.

Those are rare qualities that are so desperately needed, said Snodgrass. He was kind of the complete package.

Wildt was a seminal leader in conservation biology, [and] his prolific breakthroughs in reproductive biology and population genetics benefitted wildlife enormously, the Smithsonian wrote in a news release published at its website, nationalzoo.si.edu/conservation.

Wildt established genome resource banks and developed ground-breaking assisted reproductive technologies for giant pandas to name just one of more than 50 endangered species, the Smithsonian release states. His scientific legacy includes more than 300 scientific papers and mentorship and training of hundreds of graduate and post-doctoral students, and colleagues around the world.

One of his most groundbreaking discoveries happened when he realized that the survival plan for one species could not automatically be applied to another species, said his wife Dr. Susie Ellis, executive director of the International Rhino Foundation, which is based in Strasburg.

[H]e started out with using domestic animals as a model for wildlife, Ellis said.

However, he realized that scientists need to work within the parameters of each species needs when they develop research protocols.

Every single animal is completely different, she said. That was a huge breakthrough for him.

Another of his proudest accomplishments was his work with black-footed ferrets, which have been endangered for more than 30 years.

Only 17 of the animals remained in the wild when Wildt started working with them, she said. His team worked diligently to create artificial insemination methods, and now, she said, there are a couple thousand.

Wildt is survived by a daughter, Chelsea Taft; her husband, Beau; grandsons Noah and Jackson; stepsons, Zachary Joseph (wife Cassie), and Maxwell Joseph (wife Stephanie); and granddaughter, Everett; as well as numerous students, the Smithsonian release states.

He also is survived by his mother Louise Wildt; brother, Alan Wildt (wife Margaret) of Virginia, Illinois, and their three children.

Wildt and Ellis are canine parents to Ivy La Fleur (IVF), a female from the first litter of dogs birthed in 2015 via in vitro fertilization, the release states. Wildts SCBI team partnered with researchers at Cornell University to successfully use in-vitro fertilization (IVF) to produce live, healthy domestic puppies from cryopreserved (frozen) embryos.

For all of his professional accomplishments and successes in helping save wildlife, those closest to him remember him as a giving friend, colleague and teacher.

He was a down-home person, a brilliant scientist, Ellis said. He always had time for his students. I think thats his true legacy.

Wildts love for animals began in his childhood growing up on a rural farm in Illinois, his wife said.

His first trip to Africa really resonated with him, Ellis said. He realized then that he wanted to work with wildlife.

Wildt worked with wildlife at various zoos, in particular Omahas Henry Doorly Zoo and the Gladys Porter Zoo in Brownsville, Texas.

He did a lot of work to get to where he was, Ellis said.

In 2017, Wildt received the Smithsonian Institutions Distinguished Scholar Award in the Sciences. He received scientific achievement awards from Illinois State University, the American Association of Zoo Veterinarians and the Association of Zoos and Aquariums.

His early pioneering work with cheetahs led to the creation of the New Opportunities in Animal Health Sciences (NOAHS Center) in 1988, the release states, fostering interdisciplinary collaboration among the National Zoo, the National Institutes of Health and the National Cancer Institute to promote the health, genetic diversity and reproduction of endangered species in zoo and wild populations.

In 2005, he was one of the founding visionaries to establish the Conservation Centers for Species Survival, now based in Texas, the release states. This unique consortium was born out of an urgent need for science-driven programs and greater collaboration between facilities managing critically endangered species and private landowners.

Theres no one that comes even close to the impact that he has, said Dr. Nucharin Songsasen, acting head of the Center for Species Survival.

Calling him a pioneer in his field of population sustainability studying big herd concepts and genome population management she said the field benefited from his training of the next generation of wildlife scientists.

Thats a huge impact, she said. I just cant imagine anyone who would measure at that level.

Being a woman in a traditionally man-driven field, she said she has appreciated Wildts encouragement and leadership.

A lot of labs and offices have a culture that excludes women, she said, but Wildt wasnt like that.

I think the one thing that I really appreciate is he [was] a very good boss, Songsasen said. I would not trade him for any other boss.

Because he led by example, she said shes adopted his leadership habits in how she responds to students training under her in particular, returning emails and following up on conversations.

He set an example for all of us, she said. Its a good example that we should all follow.

The Smithsonian has set up a fund to honor Wildts work. Donations made in his memory will support his legacy and passion for educating students by bringing renowned science leaders and eminent researchers to SCBI to inspire the next generation of conservation leaders.

See original here:
Renowned scientist remembered for his way with people and animals - Northern Virginia Daily

Recommendation and review posted by Bethany Smith

If youve never heard of Crispr then get ready, because this is a technology youre likely to be hearing a lot more about in future. From genetically modified Chinese babies to foods that deliver man-made health benefits, the potential of Crispr is enormous but its implications have some deep thinkers concerned.

Announced in 2012, Crispr stand for Clustered Regularly Interspaced Short Palindromic Repeats a scientific name that doesnt do much to tell the average person what it does. However the technology represents an astonishing breakthrough, allowing scientists to essentially edit genes and change aspects of DNA in ways previously thought impossible.

Late last year, gene editing was voted to be the innovation of the last decade by readers of The Irish Times, beating out social media, the cloud and even smartphones.

So just what is it and how can something so low-key be so significant?

Crispr (pronounced crisper) allows users to edit genomes and alter DNA sequences to modify gene function. It can be used to correct genetic defects, treating and preventing the spread of diseases and improving crops. While gene editing was possible before Crispr, it cost an enormous amount of money and was relatively imprecise.

The comparison has been made that old-style gene editing could be likened to a blunt mallet while Crispr is more like a laser beam, capable of surgical accuracy at the level of DNA. The science behind this is predictably complicated, but, in essence, Crispr allows scientists to find a specific bit of DNA inside a cell and then alter that piece of DNA.

It can be used to turn genes on or off without altering their sequence and it means that scientists can alter the DNA of plants, animals and potentially human beings to do any number of things. The most significant include altering the DNA of living people to turn off genes that have resulted in them suffering from genetic disorders, or making changes to an individual persons genome so that they dont pass on any genetic defect.

In Ireland in 2018, scientists from Trinity College discovered a therapy for one of the most common soft tissue cancers using Crispr. Synovial sarcoma affects teenagers and young adults and has survival rates of less than 50 per cent.

Pre-clinical trials in mice have showed that drugs developed using information gained through Crispr were able to target cancerous cells, crucially leaving normal cells alone.

Crispr is a two or three component system that allows you to use specific targeting RNA molecules to direct an enzyme that will cut and edit DNA and in theory you can change the DNA any which way you might want to, said Dr Gerard Brien, senior research fellow researching childhood cancers in the genetics department at Trinity College.

In theory, if a disease is caused by a specific mutation, then you could fix that mutation, he said.

But its still early days. In theory, all sorts of things are possible but the practicalities of how to do these things in a way that is effective and safe were not anywhere near a point of understanding how to do that.

The problem, according to Dr Brien, is that of unwanted off target effects.

Were not yet at the point where we can make one clear and specific change and not unintentionally create other changes at the same time. Its these other unwanted changes that are the problem and that will be the stumbling block in using Crispr ethically in humans for the next twenty years, if not more, he said.

In 2020 though, Crispr has applications outside of medicine. Its already being used to alter the DNA of plants and animals to create new kinds of super-foods, genetically modified (GM) to be healthier and offer advantages to the consumer.

To date, some GM foods have been treated with suspicion by the public because their modifications have mostly been for the benefit of the farmers or retailers tomatoes that last longer on the shelf, for example but instead of this, think of coeliac-friendly GM wheat, rapeseed oil high in beneficial omega-3s and even GM potatoes that dont produce harmful cancer-causing acrylamides when fried.

Crispr is a complicated beast, however.

The problem with making changes to the DNA of a plant, animal or person is that its often quite hard to predict the full range of consequences. Tweak something here, and something over there can be affected without you realising.

Its for this reason that experiments on human beings are considered hugely unethical. But that hasnt stopped everyone from tinkering with the technology. In late 2019 Chinese biophysicist He Jiankui was jailed for three years and fined 3 million yuan (about 393,000) when he was convicted of violating a government ban on experimenting on human embryos.

He claimed to have edited the genes of a set of human twins, known by the pseudonyms Lulu and Nana, to give them protection against HIV, but was globally condemned when news of his actions broke. The Chinese court accused the man of having essentially gone on a glory run, saying the people involved in the experiment had acted in the pursuit of personal fame and gain. Theyve crossed the bottom line of ethics in scientific research and medical ethics.

The consequences of Hes actions are still unknown, but the effects will be permanent. If the twins he experimented on grow up and have children of their own, they will inherit his genetic modifications and potentially introduce a permanent change to the human genome.

One of the issues with the Chinese-born twins is that the germline was edited so they will pass their edits on to future generations and we dont know what the long-term effects of that will be, it could be that these changes to their genes could initiate cancer down the line. We just dont know, said Dr Oliver Feeney, a bioethicist and lecturer in University College Cork.

There is this thing called the precautionary principle which states that you shouldnt do something unless you have all the down-side risks guarded against and you know exactly whats going to happen. The problem is we dont do that in any other context. We generally just bulldoze through life and see what happens.

The question here is should we shape humans and the way they develop in future? Is that ethical? Most people would agree that Crispr-enabled treatments for diseases would be a good thing if theyre effective and safe, but what about enhancements? Were only at the start of the regulatory landscape that will be required to manage this.

Dr Feeney suggests that the concept of gene editing is inherently scary to some people and that can colour the way in which it is viewed.

There is a possibility that we could be too concerned about Crispr and any issues that might arise. Thats not to minimise the risks or anything, but there is a certain level of hype around this technology and perhaps also excessive fear about what it can do, he said.

Some people have gone as far as to suggest that engaging in gene editing opens the door to eugenics and a world of genetic haves and have-nots. Its ironic to consider that this is the same scenario presented in the movie Gattaca and here we are having the conversation for real 20 years later.

Read the original post:
Crispr gene-editing technology: what is it and why you need to know about it - The Irish Times

Recommendation and review posted by Bethany Smith

Do you want it locally grown, water-saving and pesticide-free? Urban agriculture might suit you, with a little help from gene editing. Zachary Lippmans team has already succeeded with Solanaceae fruit crops, optimizing tomatoes and ground-cherries for indoor production (see their paper in Nature Biotechnology).

By targeting three genes (SlER, SPG5, and SP), they made the plants display compact growth habit and early yield. The tomatoes produced were slightly smaller than the wild type, but each plant bore more fruit, and they tasted good.

Commenting the paper in the news and views section, Cathryn O Sullivan and colleagues foresee a whole CRISPR menu coming from urban agriculture in the future. It is unlikely that wheat or rice will ever be grown indoors, but urban farms will be interested in producing any plant that has high value and is eaten fresh.

First of all fruits and vegetables that grow on bushes or vines, such as tomato, strawberry, raspberry, blueberry, cucumber, capsicum, grapes, kiwifruit. Specialist crops such as hops, vanilla, saffron, coffee, and also medicinal or cosmetic crops may come next.

They think that one day even small trees (chocolate, mango, almonds) may be grown indoors. However, for indoor farming to be broadly adopted, the capital and operating costs of climate-controlled farms must be reduced, or they will benefit only the wealthiest communities.

Read the original article

Go here to read the rest:
CRISPR technology opens door to vertical farming of dozens of crops, from strawberries and cucumbers to mango and almond trees - Genetic Literacy...

Recommendation and review posted by Bethany Smith

DetailsCategory: More NewsPublished on Thursday, 20 February 2020 13:06Hits: 157

BERKELEY, CA & RICHMOND, CA, USA I February 19, 2020 I Caribou Biosciences, Inc., a leading CRISPR genome editing company, and ProMab Biotechnologies, Inc., a biotechnology CRO/CDMO specializing in antibody engineering and CAR-T development, today announced a sale and assignment agreement under which Caribou gains access to a ProMab humanized single-chain variable fragment (scFv) targeting the B Cell Maturation Antigen (BCMA) for use in allogeneic engineered cell therapies. Caribou intends to utilize this scFv in the development of its CB-011 program, an allogeneic CAR-T therapy targeting BCMA-positive tumors including multiple myeloma.

We are excited for the opportunity to have access to this highly advanced, humanized molecule and believe it will significantly advance our promising CB-011 CAR-T program, said Steven Kanner, PhD, Chief Scientific Officer of Caribou.

We anticipate that our humanized BCMA scFv will aid greatly in Caribous efforts to further its allogeneic CAR-T program, and hope our technology continues to improve the field of preclinical and clinical stage immunotherapy research by providing broad choices of validated antibodies, said John Wu, MD, Chief Executive Officer of ProMab.

Under the terms of the agreement, ProMab received an upfront payment and is eligible for royalties on net sales of licensed products containing the BCMA scFv.

About Caribou Biosciences, Inc. Caribou is a leading company in CRISPR genome editing founded by pioneers of CRISPR-Cas9 biology. The company is developing an internal pipeline of off-the-shelf CAR-T cell therapies, other gene-edited cell therapies, and engineered gut microbes. Additionally, Caribou offers licenses to its CRISPR-Cas9 foundational IP in multiple fields including research tools, internal research use, diagnostics, and industrial biotechnology. Interested companies may contact Caribou at This email address is being protected from spambots. You need JavaScript enabled to view it.. For more information about Caribou, visit http://www.cariboubio.com and follow the Company @CaribouBio. Caribou Biosciences and the Caribou logo are registered trademarks of Caribou Biosciences, Inc.

About ProMab Biotechnologies, Inc. ProMab Biotechnologies focuses on developing and commercializing mouse, rabbit, and human monoclonal antibodies as well as chimeric antigen receptor-T Cell (CAR-T) products. ProMabs CAR-T platform covers both hematological and solid cancers with intensive in vitro and in vivo pre-clinical validation designed for safer and better treatment. As a CRO in the immunology field for 19 years, ProMab offers standard laboratory procedures and animal studies for antibody discovery through the integration of the newest techniques in antibody library construction, next generation sequencing, unique humanization modeling, high-throughput screening, and artificial intelligence analysis systems. ProMab aims to out-license antibodies validated in CAR-T therapy in the preclinical stage or to bring CAR-T technologies to the early stage market of clinical study. ProMab has partnered with top biotechnology startups, medical institutions, and pharmaceutical companies to advance the development of cell therapies as well as bispecific antibodies targeting multiple cancers. For more information, visit http://www.promab.com.

SOURCE: Caribou Biosciences

Read the original:
Caribou Biosciences and ProMab Biotechnologies Announce Sale and Assignment Agreement for Humanized scFv Targeting BCMA | More News | News Channels -...

Recommendation and review posted by Bethany Smith

Though common, these big phages would have been completely missed by traditional lab techniques. It used to be that scientists could only discover viruses by first growing themand they often filtered out anything above a certain size. In science, you tend to find what you look for. The huge phages dont fit the standard conception of what a virus should be, so no one went looking for them. But Banfield used a different method, which she pioneered in the 1990s: Her team took environmental samplesscoops of soil or drops of waterand simply analyzed all the DNA within to see what popped out. And once Banfield realized that the huge phages existed, it wasnt hard to find more.

Read: Beware the Medusavirus

Her team, including researchers Basem Al-Shayeb and Rohan Sachdeva, identified huge phages in French lakes, in Tibetan springs, and on the Japanese seafloor. They found the viruses in geysers in Utah, salt from Chiles Atacama Desert, stomach samples from Alaskan moose, a neonatal intensive-care unit in Pittsburgh, and spit samples from Californian women. All of these phages have at least 200,000 DNA letters in their genome, and the largest of them has 735,000.

The team included researchers from nine countries, and so named the new viruses using words for huge in their respective languages. Hence: Mahaphage (Sanskrit), Kaempephage (Danish), Kyodaiphage (Japanese), and Jabbarphage (Arabic), but also Whopperphage (American English).

These huge phages have other strange characteristics. With so much DNA, the viruses are probably physically bigger than typical phages, which means that they likely reproduce in unusual ways. When phages infect bacteria, they normally make hundreds of copies of themselves before exploding outwards. But Banfield says that an average bacterium doesnt have enough room to host hundreds of huge phages. The giant viruses can probably only make a few copies of themselves at a timea strategy more akin to that of humans or elephants, which only raise a few young at a time, than to the reproduction of rodents or most insects, which produce large numbers of offspring.

Giant phages also seem to exert more control over their bacterial hosts than a typical virus. All viruses co-opt their hosts resources to build more copies of themselves, but the huge phages seem to carry out a much more thorough and directed takeover, Banfield says. Their target is the ribosomea manufacturing plant found in all living cells, which reads the information encoded in genes and uses that to build proteins. The huge phages seem equipped to fully commandeer the ribosome so that it ignores the hosts genes, and instead devotes itself to building viral proteins.

This takeover involves an unorthodox use of CRISPR. Long before humans discovered CRISPR and used it to edit DNA, bacteria invented it as a way of defending themselves against viruses. The bacteria store genetic snippets of phages that have previously attacked them, and use these to send destructive scissorlike enzymes after new waves of assailants. But Banfields team found that some huge phages have their own versions of CRISPR, which they use in two ways. First, they direct their own scissors at bacterial genes, which partly explains why they can so thoroughly take over the ribosomes of their hosts. Second, they seem to redirect the bacterial scissors into attacking other phages. They actually boost their hosts immune system to take out the competition.

See the rest here:
A Huge Discovery in the World of Viruses - The Atlantic

Recommendation and review posted by Bethany Smith

Audentes Therapeutics, an Astellas company, announced it is building a gene therapy manufacturing plant in Sanford, North Carolina.

The company is investing $109 million in a new 135,000-square-feet facility, with the initial phase to take place over about 18 months. It is planned to go into operation in 2021. It is expected to create more than 200 new jobs in Lee County, North Carolina. Hiring is expected to start this year.

Our investment in large-scale manufacturing has always been a cornerstone of our strategy to develop and ultimately deliver our important genetic medicines to patients as rapidly as possible, said Natalie Holles, president and chief executive officer of Audentes. This new facility in Sanford will support the next phase of our growth as we establish a robust, global supply chain and expand our therapeutic and geographic scope as a part of the Astellas group of companies. We are excited to join the vibrant biopharmaceutical research and manufacturing community that the state of North Carolina has established.

Audentes is headquartered in San Francisco and focuses on gene therapy. It was acquired by Tokyo-based Astellas Pharma in January.

No specifics were given about what the site will manufacture. In October 2019, Audentes announced positive data from ASPIRO, the clinical trial of AT132 in patients with X-Linked Myotubular Myopathy (XLMTM). AT132 is an AAV8 vector that contains a functional copy of the MTM1 gene. XLMTM is a serious, life-threatening, rare neuromuscular disease marked by extreme muscle weakness, respiratory failure and early death.

The company indicates it hopes to submit a Biologics License Application (BLA) for AT132 to the U.S. Food and Drug Administration (FDA) later this year.

An announcement ceremony was held in the industrial shell building the company is buying in the Central Carolina Enterprise Park. It is about 45 miles southwest of Raleigh.

Gov. Roy Cooper stated, With our powerhouse research centers and highly skilled workforce, biotech pioneers recognize North Carolinas role as a leader in the life sciences. Lee County is a perfect fit for Audentes as they seek to become a global leader in genetic medicines.

The employees at the new factory are expected to earn an average salary of $83,900, which is a little over twice the Lee County average of $41,800. If Audentes hits hiring milestones, it will qualify for a state Job Development Investment Grant worth up to $3.7 million.

The county and the city of Sanford are also offering $5.7 million incentives, which includes almost $400,000 in training support from the North Carolina Community College System.

Audentes chose the location over California, Massachusetts and Colorado.

In every interaction, I was impressed with Audentes patient-centric approach to developing their AAV-based gene therapy to transform the lives of affected patients and families, said Laura Rowley, NCBiotechs director of life science economic development. She led the Centers outreach activity with Audentes. Their decision to grow in North Carolina reflects the Research Triangle regions specialized training capabilities and strengths in gene therapy and biomanufacturing. The passion and focus of the Audentes team makes me confident that they will be an outstanding addition to North Carolinas gene therapy community.

Audentes is acting as the Center of Excellence for Astellas newly founded Genetic Regulation Primary Focus.

Audentes Therapeutics is joining one of the nations top life science clusters, said Anthony M. Copeland, North Carolinas Commerce Secretary. North Carolina has the largest biomanufacturing workforce in the nation and a growing concentration of gene therapy scientists, researchers and workers.

The site of the new plant is quite close to Pfizers new gene therapy campus, which is under construction. That $600 million research and manufacturing facility has a 230-acre campus in Sanford and will employ 340 people.

Read more:
Audentes to Build $109 Million Gene Therapy Factory in North Carolina - BioSpace

Recommendation and review posted by Bethany Smith

Image caption Matthew Wood hopes the gene therapy will help him keep his remaining vision

A new gene therapy has been used to treat patients with a rare inherited eye disorder which causes blindness.

It's hoped the NHS treatment will halt sight loss and even improve vision.

Matthew Wood, 48, one of the first patients to receive the injection, told the BBC: "I value the remaining sight I have so if I can hold on to that it would be a big thing for me."

The treatment costs around 600,000 but NHS England has agreed a discounted price with the manufacturer Novartis.

Luxturna (voretigene neparvovec), has been approved by The National Institute for Health and Care Excellence (NICE), which estimates that just under 90 people in England will be eligible for the treatment.

The gene therapy is for patients who have retinal dystrophy as a result of inheriting a faulty copy of the RPE65 gene from both parents. The gene is important for providing the pigment that light sensitive cells need to absorb light. Initially this affects night vision but eventually, as the cells die, it can lead to complete blindness.

An injection is made into the back of the eye - this delivers working copies of the RPE65 gene. These are contained inside a harmless virus, which enables them to penetrate the retinal cells. Once inside the nucleus, the gene provides the instructions to make the RPE65 protein, which is essential for healthy vision.

Matthew Wood started losing his sight as a child, and is now registered blind. However, he does have some peripheral vision and can detect large objects and bright lights. He told the BBC: "Since I was a child I was continually told there was no treatment for this condition, so it's amazing to receive this gene therapy."

Mr Wood, from London, had his right eye treated during an hour-long operation at the John Radcliffe Hospital in Oxford.

His left eye will be injected in a few weeks. The surgery was carried out by Prof Robert MacLaren, who has pioneered research into gene therapies for preventing blindness.

He told the BBC: "This is very exciting - this is the first approved NHS gene therapy for an eye disease, but there are opportunities to use gene therapy to treat other diseases in future, not only in the eye."

The treatment is only suitable for patients who have some remaining vision. It should bring the biggest benefits to children with RPE65 retinal dystrophy, as it could halt sight loss before permanent damage is done.

It is not known how long the benefits of the treatment will last, but it's thought it could be several decades.

Jake Ternent, 23, from Durham, had his gene therapy at Moorfields Eye Hospital in London.

Like Matthew Wood, he is registered blind, but has some limited sight. He told the BBC: "I hope the treatment could improve my night vision, and possibly even my day vision, which would be incredible. I feel lucky and privileged to get this on the NHS."

Prof James Bainbridge - from Moorfields Eye Hospital - who treated Jake, told the BBC: "To be at the point now where we are able to offer this treatment on the NHS, is truly remarkable. This is the first example of what's anticipated to be a whole new generation of treatments."

It will take a month or two before Matthew and Jake know what changes the gene therapy has made to their vision. But even if it simply prevents further sight loss, both say they will be delighted.

Professor Stephen Powis, NHS medical director, said: "Loss of vision can have a devastating effect, particularly for children and young people, but this truly life-changing treatment offers hope to people with this rare and distressing condition."

Follow Fergus on Twitter.

More here:
Gene therapy to halt rare form of sight loss - BBC News

Recommendation and review posted by Bethany Smith

Industry leaders, patient advocates, researchers unite to maximize the incredible potential of transformative gene therapies

WASHINGTON--(BUSINESS WIRE)-- The Institute for Gene Therapies (IGT) launched today with a focus on advocating for a modernize the U.S. regulatory and reimbursement framework so that gene therapies can deliver their significant potential to patients. IGT will educate stakeholders across the healthcare community about the transformational nature of gene therapies and advocate for policies that help ensure patients who need them can benefit from them.

Gene therapy is poised to change human health as we know it. By altering non-functioning genes or replacing absent ones, gene therapies have the potential to reshape the way thousands of diseases are treated with long-lasting effects for patients. The first of these transformative therapies have already been approved by the U.S. Food and Drug Administration (FDA) and hundreds more are currently being studied in clinical trials for rare and common diseases, including many types of cancer, neuromuscular diseases, blood disorders and infectious diseases, among others.

Many crippling conditions like Charcot-Marie-Tooth, which I was diagnosed with before the age of two take hold at a very young age, cut lives far too short or cause ongoing daily suffering, said Susan Ruediger, CEO of the CMT Research Foundation (CMTRF) and member of the IGT Patient Advocacy Advisory Council. Like so many diseases, CMT currently has no cure. I am proud to stand with other leading patient advocates, members of the research community and companies that are developing gene therapies to help ensure patients can fully realize the benefits of these giant leaps toward treatments and cures.

Gene therapies are fundamentally different from traditional pharmaceutical and biologic medicines in that they target the cause of the disease at the DNA level to create a change in the body. Further, some gene therapies are designed to be one-time treatments that offer life-long benefits. Today, the vast majority of medicines help manage the symptoms of disease over time rather than address or halt diseases at their root. The U.S. healthcare system from the drug approval process to the way treatments are paid for reflects this reality. The existing regulatory and reimbursement structures, which were established and adjusted over time to accommodate pharmaceutical and biologic medicines, need revisiting in light of gene therapies and their significant potential.

The incredible scientific advancements in this space present unique opportunities to directly improve and save the lives of patients suffering from debilitating diseases, said IGT Chairman, and former Congressman Erik Paulsen. This is not some far-off future patients are already benefiting from the first FDA-approved gene therapies. But we need policy to move faster toward this new reality where we can treat the causes of many diseases. The Institute for Gene Therapies and our members believe unique regulatory and reimbursement structures need to be established, novel development pathways need to be embraced and new value-based arrangements need to be tested.

As part of IGTs effort, experts from across the healthcare system will work together to ensure health policies reflect the latest medical advances, remove barriers that hinder patient access to gene therapies and advocate for sustainable, long-term solutions. IGT will work to ensure a greater understanding about the value gene therapies bring to patients, families, the healthcare system and our society so that gene therapies can achieve their full potential.

About the Institute for Gene Therapies

The Institute for Gene Therapies (IGT) works with stakeholders across the healthcare system to advocate for a modernized regulatory and reimbursement framework that encourages the development of transformative gene therapies and promotes patient access. Members of our advisory councils include Johnson & Johnson, PTC Therapeutics, Sarepta Therapeutics, Spark Therapeutics, Patient Advocate Foundation, Cure SMA, CMT Research Foundation, American Autoimmune Related Diseases Association (AARDA), Khrystal Davis, Founder of Texas Rare Alliance, Jenn McNary, Founder of One Rare, Seth Rotberg, Co-Founder and Head of Strategy & Engagement of Our Odyssey, Rolf Benirschke, Patient Advocate for Crohns disease, ulcerative colitis, colorectal and bladder cancer, Friedreichs Ataxia Research Alliance, and Foundation Fighting Blindness. For more information, visit gene-therapies.org and follow us on Twitter @gene_therapies

View source version on businesswire.com: https://www.businesswire.com/news/home/20200219005526/en/

Here is the original post:
New Institute Launched to Ensure the US Healthcare System Is Ready for Gene Therapies - BioSpace

Recommendation and review posted by Bethany Smith

Scientists have explored the effectiveness of replacing mutated genes in mice with congenital blindness.

Describing their findings in Nature Communications, researchers highlighted that replacing a mutated sequence in blind mice resulted in approximately 10% of photoreceptors being rescued.

Following the procedure, the light sensitivity and visual acuity of the mice improved.

The new approach is an alternative strategy to gene supplementation, which has limitations when treating patients with defects in larger genes.

Koji Nishiguchi, from Tohoku Universitys department of advanced ophthalmic medicine, explained that the new technique enables the replacement of a mutated sequence with its healthy counterpart.

The platform paves the way for treating patients with mutations in larger genes, which comprise the vast majority of those with inherited retinal degeneration. Furthermore, a similar approach can be applied to treat almost any ocular and non-ocular inherited conditions, he shared.

The research team are developing the genome editing platform for application in patients with retinitis pigmentosa. A clinical trial could be undertaken by 2025.

Image credit: Pixabay/Arek Socha

See the article here:
Mice display improvements in vision following gene therapy - AOP

Recommendation and review posted by Bethany Smith

Abstract

Vascular dysfunction is a typical characteristic of aging, but its contributing roles to systemic aging and the therapeutic potential are lacking experimental evidence. Here, we generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome (HGPS) LmnaG609G mutation, called progerin. The Lmnaf/f;TC mice with progerin expression induced by Tie2-Cre exhibit defective microvasculature and neovascularization, accelerated aging, and shortened life span. Single-cell transcriptomic analysis of murine lung endothelial cells revealed a substantial up-regulation of inflammatory response. Molecularly, progerin interacts and destabilizes deacylase Sirt7; ectopic expression of Sirt7 alleviates the inflammatory response caused by progerin in endothelial cells. Vascular endotheliumtargeted Sirt7 gene therapy, driven by an ICAM2 promoter, improves neovascularization, ameliorates aging features, and extends life span in Lmnaf/f;TC mice. These data support endothelial dysfunction as a primary trigger of systemic aging and highlight gene therapy as a potential strategy for the clinical treatment of HGPS and age-related vascular dysfunction.

Aging represents the largest risk factor for many age-related diseases, as exemplified by cardiovascular diseases (CVDs) (1). The blood vessel consists of the tunica intima [composed of endothelial cells (ECs)], the tunica media [composed of vascular smooth muscle cells (VSMCs)], and the tunica adventitia (consisting of connective tissue) (2). The endothelium separates the vessel wall from blood flow and has an irreplaceable role in regulating vascular tone and homeostasis. Age-related functional decline in ECs and VSMCs is a main cause of CVDs (3). ECs secrete various vasodilators and vasoconstrictors that act on VSMCs and induce blood vessel contraction and relaxation (4). For instance, nitric oxide (NO) is synthesized from l-arginine by endothelial NO synthase (eNOS) and then released on VSMCs to induce blood vessel relaxation (5). When ECs become senescent or dysfunctional, vasoconstrictive, procoagulative, and proinflammatory cytokines are released; this effect reduces NO bioavailability and, in turn, increases vascular intimal permeability and EC migration (6). Despite advances in the understanding of mechanisms of endothelial dysfunction, it is unclear whether it directly triggers organismal aging.

Accumulating evidences suggest that the mechanisms underlying physiological aging are similar to those governing Hutchinson-Gilford progeria syndrome (HGPS)a premature aging syndrome in which affected patients typically succumb to CVDs (7). HGPS is predominantly caused by an a.c. 1824 C>T, p. G608G mutation in LMNA gene, which activates an alternate splicing event and generates a 50amino acid truncated form of Lamin A, referred to as progerin (8). The murine LmnaG609G, which is equivalent to LMNAG608G in humans, causes aging phenotypes resembling HGPS (9). It has been shown that progerin targets SMCs and causes blood vessel calcification and atherosclerosis (10, 11). Recent work by two groups showed that SMC-specific progerin knock-in (KI) mice are healthy and have a normal life span but suffer from blood vessel calcification, atherosclerosis, and shortened life span when crossed to Apoe/ mice (12, 13). In contrast to SMCs, the contributing roles of the vascular endothelium (VE) to systemic/organismal aging are still elusive. To address these issues, we generated a conditional progerin (LmnaG609G) KI model, i.e., Lmnaf/f mice. In combination with E2A-Cre and Tie2-Cre mice, in which the expression of Cre is ubiquitous including germ cells (14) or driven by the endothelial-specific Tie2 promoter (15), we aimed to investigate the roles of VE dysfunction to systemic aging and the targeting potential for the clinical treatment of HGPS.

To study the mechanism of VE aging, we generated a mouse model of conditional progerin KI, in which the LmnaG609G mutation, equivalent to HGPS LMNAG608G, was flanked with loxP sites, i.e., Lmnaf/f mice (fig. S1A). The Lmnaf/f mice were crossed to E2A-Cre mice, in which the Cre recombinase is ubiquitously expressed including germ cells, to generate LmnaG609G/G609G and LmnaG609G/+ mice. Progerin was ubiquitously expressed in LmnaG609G/G609G and LmnaG609G/+ mice, which recapitulated many progeroid features found in HGPS, including growth retardation and shortened life span (fig. S1, B to D).

To understand primary alterations in the VE, we isolated CD31+ murine lung ECs (MLECs) (16) from three pairs of LmnaG609G/G609G (G609G) and Lmnaf/f (Flox) mice by fluorescence-activated cell sorting (FACS) (Fig. 1A) and performed 10 Genomics single-cell RNA sequencing. We recovered 6004 cells (4137 from G609G and 1867 from Flox mice) and used the k-means clustering algorithm to cluster the cells into four groups (Fig. 1B). As expected, one group exhibited high Cd31, Cd34, and Cdh5 expression and thus largely represented MLECs. The other three groups, copurified with CD31+ MLECs by FACS, showed relatively lower Cd31 expression at the mRNA level (>10-fold lower than MLECs) but high Cd45 expression (fig. S2). Further analysis revealed that these clusters most likely contained B lymphocytes (B-like) with high Cd22, Cd81, and Ly6d expression; T lymphocytes (T-like) with high Cd3d, Cd3e, and Cd28 expression; and macrophages (M-like) with high Cd14, Cd68, and Cd282 expression (Fig. 1C). Most of the marker gene expression levels were comparable between G609G and Flox mice, except for Cd34 and Icam1, which were significantly elevated in G609G ECs, and Cd14 and Vcam1, which were increased in G609G M-like cells (Fig. 1D). Of note, Icam1 and Vcam1 are among the most conserved markers of endothelial senescence and atherosclerosis (17). Thus, we established an Lmnaf/f conditional progerin KI mouse model and revealed a unique EC population for mechanistic study.

(A) Purity analysis of sorted CD31+ MLECs by FACS. SSC, side scatter; FSC, forward scatter; PE, phycoerythrin. (B) t-Distributed stochastic neighbor embedding (t-SNE) projection of CD31+ cells revealed four clusters: ECs (green), B lymphocytes (B-like; orange), T lymphocytes (T-like; blue), and macrophages (M-like; red). (C) Marker gene expression in the four clusters: ECs (Cd31, Cd34, and Cdh5), B-like (Ly6d, Cd22, and Cd81), T-like (Cd3d, Cd3e, and Cd28), and M-like (Cd14, Cd68, and Cd282). (D) Heatmap showing marker gene expression levels in LmnaG609G/G609G (G609G) and Lmnaf/f (Flox) mice.

Of the four clusters of CD31+ MLECs, ECs and M-like cells showed high levels of p21Cip1/Waf1 (fig. S2A), a typical senescence marker (18). This finding suggests that these cells are the main target of progerin in the context of aging. A previous study reported that M-specific progerin, achieved by crossing Lmnaf/+ to Lyz-Cre mice, caused minimal aging phenotypes (12), implicating that M might have only a minor role in organismal aging. We thus focused on ECs for further analysis. We recovered 899 and 445 ECs from E2A and Flox mice, respectively (Fig. 2A). Genes with >1.5-fold change in expression between these mice were chosen for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. We observed a significant enrichment in the pathways that regulate chemotaxis, immune responses in malaria and Chagas diseases, inflammatory bowel disease, and rheumatoid arthritis and pathways essential for cardiac function (Fig. 2, B to D). To confirm this observation and to exclude paracrine effects from other cell types, we overexpressed progerin in human umbilical vein ECs (HUVECs) and analyzed representative genes by quantitative polymerase chain reaction (PCR). Most of the examined genes, e.g., IL6, IL8, IL15, CXCL1, IL1, etc., were significantly up-regulated upon ectopic progerin overexpression (Fig. 2E). Together, these data suggest that progerin causes an inflammatory response in VE, which might lead to systemic aging.

(A) t-SNE projection of LmnaG609G/G609G (G609G; green) and Lmnaf/f (Flox; orange) CD31+ MLECs according to transcriptomic data. (B to D) GO and KEGG pathway enrichment of differentially expressed genes between G609G and Flox cells. LmnaG609G/G609G MLECs show enrichment in genes that regulate the inflammatory response (C) and genes related to heart dysfunction (D). FC, fold change; FDR, false discovery rate. (E) Quantitative PCR analysis of altered genes observed in (C) and (D) in HUVECs with ectopic expression of progerin or wild-type LMNA. Data represent means SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 (Students t test).

To test whether the VE dysfunction has essential roles in systemic aging, we crossed Lmnaf/f mice to a Tie2-Cre line to generate Lmnaf/f;TC mice, in which the expression of Cre recombinase is driven by the promoter/enhancer of endothelial-specific Tie2 gene (15). Single-cell transcriptome analysis confirmed that Tie2 was mainly detected in ECs (fig. S2B). Consistently, progerin was observed in the VE of Lmnaf/f;TC, but not in that of Lmnaf/f control mice or other tissues (fig. S3). VE-specific progerin induced intima-media thickening in Lmnaf/f;TC mice, in a similar manner to total KI mice, i.e., LmnaG609G/G609G mice (Fig. 3, A and B). We performed functional analysis of the VE based on acetylcholine (ACh)regulated vasodilation. ACh-induced thoracic aorta relaxation was significantly compromised in Lmnaf/f;TC mice (Fig. 3C). Similar defects were observed in LmnaG609G/G609G and LmnaG609G/+ mice (Fig. 3D and fig. S4), where progerin was expressed in both ECs and SMCs (12). To gain more evidence supporting VE-specific dysfunction, we examined thoracic aorta relaxation induced by sodium nitroprusside (SNP), which is an SMC-dependent vasodilator. Little difference was observed in thoracic aorta vasodilation in LmnaG609G/G609G and LmnaG609G/+ compared to Lmnaf/f control mice (Fig. 3E and fig. S4), supporting the notion that the VE dysfunction is a key contributor of vasodilation defects in progeria mice. As NO is the most potent vasodilator (19), we examined eNOS levels in the thoracic aorta of Lmnaf/f;TC and Lmnaf/f control mice. As expected, the level of eNOS was significantly reduced in Lmnaf/f;TC mice compared to Lmnaf/f control mice (Fig. 3F). Thus, the data confer a VE-specific dysfunction in progeria mice.

(A and B) Hematoxylin and eosin staining of thoracic aorta sections from (A) Lmnaf/f;TC and (B) LmnaG609G/G609G and Lmnaf/f control mice showing intima-media thickening. Scale bar, 20 m. (C) ACh-induced thoracic aorta vasodilation in Lmnaf/f;TC and Lmnaf/f control mice. **P < 0.01. 5-HT, 5-hydroxytryptamine. (D) ACh-induced thoracic aorta vasodilation in LmnaG609G/G609G and control mice. **P < 0.01. (E) SNP-induced thoracic aorta vasodilation in LmnaG609G/G609G and control mice. (F) eNOS level in thoracic aorta sections from Lmnaf/f;TC and control mice. Scale bar, 20 m. (G) Immunofluorescence staining (left) and quantification (right) of CD31+ gastrocnemius muscle in Lmnaf/f;TC and Lmnaf/f mice. Scale bar, 50 m. DAPI, 4,6-diamidino-2-phenylindole. (H) CD31 immunofluorescence staining in Lmnaf/f;TC and Lmnaf/f liver. Scale bar, 50 m. (I) Representative microcirculation images (left) and quantification of blood flow recovery (right) following hindlimb ischemia in Lmnaf/f;TC and Lmnaf/f mice. (J) Representative transverse sections and quantification of CD31+ gastrocnemius muscle 14 days after femoral artery ligation. Scale bar, 50 m. All data represent means SEM. P values were calculated by Students t test. Photo credits: Shimin Sun, School of Life Sciences, Shandong University of Technology; Medical Research Center, Shenzhen University (A, B, F, H, and J); Weifeng Qin, Medical Research Center, Shenzhen University (G and I).

The reduced capillary density and neovascularization capacity are both characteristics of endothelial dysfunction (1). We examined the microvasculature in various tissues of Lmnaf/f;TC mice by immunofluorescence staining. We observed a significant loss in CD31+ ECs in Lmnaf/f;TC mice compared to controls (Fig. 3, G and H). We further examined ischemia-induced neovascularization ability in Lmnaf/f;TC mice following femoral artery ligation. Limb perfusion after ischemia was significantly blunted in Lmnaf/f;TC mice compared to controls (Fig. 3I). Histological analysis confirmed that the defect in blood flow recovery in Lmnaf/f;TC mice was a reflection of an impaired ability to form new blood vessels in the ischemic region (Fig. 3J). Together, Lmnaf/f;TC mice are characterized by a loss of ECs, a reduced capillary density, and defective neovascularization capacity.

The single-cell transcriptome implicates heart dysfunction in LmnaG609G/G609G mice (Fig. 2). A correlation with gene alterations associated with atherosclerosis and osteoporosis was obvious in LmnaG609G/G609G ECs (the Online Mendelian Inheritance in Man; https://omim.org) (fig. S5). We thus reasoned that endothelial-specific dysfunction might be enough to trigger systemic aging. Notably, atherosclerosis was prominent in Lmnaf/f;TC mice (aorta atheromatous plaque observed in all nine examined mice; Fig. 4A), as well as severe fibrosis in the arteries and hearts (Fig. 4, B and C); both are typical features of aging. Moreover, the heart/body weight ratio was significantly increased in Lmnaf/f;TC compared to Lmnaf/f control mice (Fig. 4D), indicating dilated cardiomyopathy (20). Echocardiography confirmed that heart rate, cardiac output, left ventricular ejection fraction, and fractional shortening were significantly reduced in 7- to 8-month-old Lmnaf/f;TC compared to Lmnaf/f control mice. The running endurance was largely compromised in Lmnaf/f;TC mice (Fig. 4E), which is likely a reflection of amyotrophy. Moreover, the microcomputed tomography (CT) identified a decrease in trabecular bone volume/tissue volume, trabecular thickness, and trabecular number but an increase in trabecular separation in Lmnaf/f;TC mice (Fig. 4F), indicative of osteoporosis, which is an important hallmark of systemic aging (21). The VE-specific dysfunction not only accelerated aging in various tissues/organs but also shortened the median life span of Lmnaf/f;TC mice (24 weeks) to a similar extent to LmnaG609G/G609G mice (21 weeks) (Fig. 4G). LmnaG609G/G609G mice suffered from body weight loss roughly from 8 weeks of age, while Lmnaf/f;TC mice only showed a slight drop in body weight (Fig. 4H), suggesting that body weight loss itself is a less likely primary causal factor to progeria compared to endothelial dysfunction. Together, these results implicate that endothelial dysfunction, at least in progeria, acts as a causal factor of systemic aging.

(A to C) Masson trichrome staining showing an atheromatous plaque in the aorta (A), SMC loss (B), and cardiac fibrosis (C) in Lmnaf/f;TC mice. Scale bar, 20 m. (D) Heart weight and echocardiographic parameters, including heart rate, cardiac output, left ventricular (LV) ejection fraction (LVEF), and left ventricular ejection shortening (LVFS). *P < 0.05, Lmnaf/f;TC versus Lmnaf/f mice. (E) Decreased running endurance in Lmnaf/f;TC mice. ***P < 0.001. (F) Micro-CT analysis showing a decrease in trabecular bone volume/tissue volume (BV/TV), trabecular number, and trabecular thickness and an increase in trabecular separation in Lmnaf/f;TC mice. *P < 0.05, Lmnaf/f;TC versus Lmnaf/f mice. (G) Life span of LmnaG609G/G609G, LmnaG609G/+, Lmnaf/f;TC, and Lmnaf/f mice. (H) Body weight of male LmnaG609G/G609G, LmnaG609G/+, Lmnaf/f;TC, and Lmnaf/f mice. *P < 0.05, Lmnaf/f;TC versus Lmnaf/f mice; ***P < 0.001, LmnaG609G/G609G versus Lmnaf/f mice. All data represent means SEM. P values were calculated by Students t test, except that statistical comparison of the survival data was performed by log-rank test. Photo credits: Weifeng Qin, Medical Research Center, Shenzhen University (A and B); Shimin Sun, School of Life Sciences, Shandong University of Technology; Medical Research Center, Shenzhen University (C).

Loss of Sirt7, an NAD+ (nicotinamide adenine dinucleotide)dependent deacylase, causes heart dysfunction with systemic inflammation and accelerates aging (22, 23). We noticed defective neovascularization in Sirt7 knockout mice (Fig. 5A). Knockdown of Sirt7 up-regulated the levels of interleukin-1 (IL-1) and IL6 in HUVECs, as determined by Western blotting and real-time PCR (Fig. 5, B and C). Significantly, the protein level of Sirt7 was reduced almost 50% in Lmnaf/f;TC MLECs (Fig. 5D). By contrast, the levels of Sirt6 and Sirt1 were hardly decreased in Lmnaf/f;TC MLECs. Furthermore, co-immunoprecipitation revealed that Lamin A interacted with Sirt7, which was significantly enhanced in the case of progerin (Fig. 5E). FLAG-SIRT7 was polyubiquitinated, which was enhanced in the presence of progerin compared with Lamin A (Fig. 5F). Ectopic expression of progerin in human embryonic kidney (HEK) 293 accelerated SIRT7 protein degradation, which was inhibited by MG132 (a proteasome inhibitor) (Fig. 5G). These data suggest that accumulation of progerin destabilizes Sirt7 by proteasomal pathway in progeria cells.

(A) Quantification of blood flow recovery following hindlimb ischemia in Sirt7/ and Sirt7+/+ mice. (B) Left: Representative immunoblots showing indicated protein levels in HUVECs treated with si-SIRT7 or scramble (Scram). Right: Quantification of relative protein levels. *P < 0.05 and **P < 0.01, small interfering RNA (siRNA) versus Scram. GAPDH, glyceraldehyde-3-phosphate dehydrogenase. (C) Real-time PCR analysis of the indicated gene expression in HUVECs treated with si-SIRT7 or Scram. *P < 0.05, siRNA versus Scram. (D) Left: Representative immunoblots showing indicated sirtuin protein levels in FACS-sorted MLECs. Right: Quantification of relative protein levels. *P < 0.05. Note that down-regulated Sirt7 but rather up-regulated Sirt6 and hardly changed SIRT1 in Lmnaf/f;TC MLECs. (E) Left: Co-immunoprecipitation (IP) experiments showing hemagglutinin (HA)SIRT7 in antiFLAGLamin A and antiFLAG-progerin immunoprecipitates. Right: Quantification of relative protein levels. *P < 0.05. (F) Left: Representative immunoblots showing polyubiquitinated SIRT7, which was up-regulated in the presence of progerin but rather down-regulated in the presence of Lamin A. Right: Quantification of relative protein levels. *P < 0.05. (G) Representative immunoblots showing SIRT7 protein levels in the presence of Lamin A or progerin in HEK293 cells treated with cycloheximide (CHX) and/or MG132 (M). Quantification of relative SIRT7 protein levels was shown. *P < 0.05, progerin versus Lamin A. All data represent means SEM. P values were calculated by Students t test. Photo credit: Xiaolong Tang, Medical Research Center, Shenzhen University (B, D, E, F, and G).

We reasoned that Sirt7 might underlie the VE dysfunction in progeria mice. To test this hypothesis, we first examined whether ectopic Sirt7 could rescue the exacerbated inflammatory response in HUVECs. As shown, overexpression of SIRT7 significantly down-regulated the expression of multiple inflammatory genes such as IL1 (Fig. 6A). To test the in vivo function of Sirt7 in defective neovascularization, we generated a recombinant AAV serotype 1 (rAAV1) cassette with Sirt7 gene expression driven by a synthetic ICAM2 promoter (IS7O), which ensures VE-specific expression (24, 25). As shown, on-site injection of IS7O at a dose of 1.25 1010 viral genome-containing particles (vg)/50 l significantly improved blood vessel formation in Lmnaf/f;TC mice (Fig. 6B). The ectopic expression of Sirt7 and the increase in CD31-labeled ECs were evidenced by fluorescence confocal microscopy in ECs of regenerated blood vessels (Fig. 6, C and D).

(A) Real-time PCR analysis of genes that are aberrantly up-regulated in progerin-overexpressing HUVECs upon overexpression of SIRT7. *P < 0.05, **P < 0.01, and ***P < 0.001. (B) Neovascularization assay in Lmnaf/f;TC mice with hindlimb ischemia, treated with or without IS7O particles. **P < 0.01. (C) Immunofluorescence microscopy analysis of FLAG-SIRT7 and CD31 expression in gastrocnemius muscle 14 days after femoral artery ligation. Scale bar, 25 m. (D) Percent CD31+ ECs in Lmnaf/f;TC mice treated with or without IS7O particles. ***P < 0.001. (E) Representative immunofluorescence images of the liver, aorta, and muscle of Lmnaf/f;TC mice after IS7O therapy, showing CD31+ ECs with FLAG-SIRT7 expression. Scale bar, 50 m. (F) Representative immunoblots showing expression of FLAG-SIRT7 in aorta and WBMCs. Note that FLAG-SIRT7 was merely detected in WBMCs. (G) Life span of IS7O-treated and untreated Lmnaf/f;TC and LmnaG609G/+ mice. (H) Body weight of IS7O-treated and untreated Lmnaf/f;TC and Lmnaf/f mice. All data represent means SEM. P values were calculated by Students t test, except that the statistical comparison of survival data was performed by log-rank test. Photo credits: Shimin Sun, School of Life Sciences, Shandong University of Technology; Medical Research Center, Shenzhen University (C and E); Xiaolong Tang, Medical Research Center, Shenzhen University (F).

We next asked whether IS7O could ameliorate premature aging and extend life span. To this end, the IS7O particles were injected via tail vein from 21 weeks of age, when progeria mice start to die. The injection was repeated every other week at a concentration of 5 1010 vg/200 l per mouse. While all untreated mice died before 34 weeks of age, most IS7O-treated mice were still alive at the age of 44 weeks, when they were euthanized for histological analysis. The ectopic expression of FLAG-SIRT7 was observed in the ECs of liver, muscle, and aorta, but not in whole bone marrow cells (WBMCs), determined by fluorescence microscopy and/or Western blotting (Fig. 6, E and F). The median life span was extended by 76%from 25 to >44 weeks (Fig. 6G). The age-related body weight loss was slightly rescued upon IS7O therapy in Lmnaf/f;TC mice (Fig. 6H). These data suggest that progerin-caused VE dysfunction and systemic aging are partially, if not entirely, attributable to Sirt7 decline.

Mounting evidence supports the idea that endothelial dysfunction is a conspicuous marker for vascular aging and CVDs (2628). However, the fundamental question whether VE dysfunction causally triggers systemic aging remains. The heterogeneity of vascular cells and their close communication with the bloodstream render it difficult to understand the primary function of the VE. The murine LmnaG609G mutation, equivalent to the LMNAG608G found in humans with HGPS, causes premature aging phenotypes in various tissues and organs, thus providing an ideal model for studying aging mechanisms at both tissue and organismal levels. Data from the LmnaG609G model suggest that SMCs are the primary cause of vascular diseases, such as atherosclerosis (10, 11). A recent study showed that specific expression of LmnaG609G in SMCs causes atherosclerosis and shortens life span in atherosclerosis-prone Apoe/ mice (12). We used Tie2-Cre line to generate the VE-specific LmnaG609G mouse model. Lmnaf/f;TC mice exhibited vascular dysfunction, accelerated aging, and a shortened life span to a similar extent to the whole-body LmnaG609G model. Tie2 expression was reported not only in ECs but also in hematopoietic lineages (29). Our single-cell transcriptomic data identified Tie2 transcripts mainly in MLECs instead of B-, T-, or M-like cells. When a synthetic ICAM2 promoter was used to drive ectopic expression of FLAG-SIRT7 in the rescue experiments, ectopic FLAG-SIRT7 was successfully detected in ECs of the aorta, muscle, and liver but hardly detected in WBMCs. Therefore, Tie2-driven progerin expression combined with synthetic ICAM2-drivern SIRT7 rescue largely ensures the EC-specific contribution in systemic aging. Of note, although the number and function of hematopoietic stem cells decline in another progeria model, Zmpste24/ mice (30), little effect was observed when healthy hematopoietic progenitor cells were transplanted to Zmpste24/ mice in the context of systemic aging. Recently, Hamczyk et al. (12) found that knocking in the LmnaG609G allele in macrophages mediated by LysM-Cre merely affects aging and life span. Therefore, our data strongly suggest that, as the largest secretory organ (3), VE is pivotal in regulating systemic aging and longevity. In support of our findings, Foisner et al. (31) reported that VE-cadherin promoter-driven expression of progerin in a transgenic line causes cardiovascular abnormalities and shortens life span.

One limitation in the understanding of mechanisms of VE dysfunction is the vascular cell heterogeneity and the lack of appropriate in vitro system for ECs. Here, we took advantage of single-cell RNA sequencing technique to analyze the transcriptomes of MLECs. Unexpectedly, although >95% purity was achieved by FACS, MLECs isolated by CD31 immunofluorescence labeling turned out to be a mixture of cells, including ECs and T-, B-, and M-like cells. Although enriched by FACS, these non-ECs expressed low level of CD31 mRNA, raising the possibility that cell surface proteins such as CD31 T-, B-, and M-like cells might be obtained from neighbor ECs via intercellular protein transfer (32). Nevertheless, these findings suggest that one cannot just purify CD31+ cells and pool them together for mechanistic study, because one might arrive at a misleading conclusion. We compared the expression of genes that are associated with atherosclerosis, arthritis, heart failure, osteoporosis, or amyotrophy (the Online Mendelian Inheritance in Man; https://omim.org) between progeroid and control in all four clusters. An obvious alteration of these genes/pathways was observed mainly in ECs and M-like cells (fig. S2). At the current stage, it is hard to separate cell-autonomous and paracrine effects among different cell populations. In the future, it would be worthwhile to do an analysis in Lmnaf/f;TC MLECs. The data will be useful to study the paracrine effect of ECs on other cell populations.

Since the identification of the causal link between LMNA G608G mutation and HGPS, numerous efforts have been put on the development of treatment for HGPS. Farnesyltransferase inhibitors (33), resveratrol, and N-acetyl cysteine (30) treatment alleviate premature aging features and extend life span in progeria murine models. Rapamycin (34) and metformin (35) incubation rescue senescence in HGPS cells. On the basis of these notions, patients with HGPS taking a farnesyltransferase inhibitor, lonafarnib, in a clinical trial showed significant improvement of health status, reduction of mortality rate, and a potential extension of life span (about 1 to 2 years) (36). Taking advantage of gene therapy and the dispensable role of Lamin A, morpholino oligos (9), and CRISPR-Cas9 designs (37, 38), which prevent Lamin A/progerin generation, can alleviate aging features and extend life span from 25 to 40% in progeria mice. However, considering the indispensable function of Lamin A in humans, these genome-modifying strategies need further experimentation before potential clinical application. Here, applying a different strategy, we showed that rAAV1-SIRT7 (IS7O), targeting dysfunctional VE, largely ameliorates progeroid features and almost doubles the median life span (from 25 to >44 weeks). To our best knowledge, this is the most marked rescue of progeria in a mouse model via gene therapy. Given that SIRT7 elicits deacylase activity to modulate cellular functions (22, 23), it is worthwhile to identify small molecules that specifically target SIRT7 activity for therapeutics in the future. Resveratrol is a potential activator of SIRT1, as well as SIRT7 (39), and has protective effects on vascular function and blood pressure (40). Further depicting the relationship of SIRT7 and resveratrol in the regulation of vascular function would help in seeking leading compounds of SIRT7 specific activators.

Collectively, we reveal VE dysfunction as a primary trigger of systemic aging and as a risk factor for age-related diseases such as atherosclerosis, heart failure, and osteoporosis. Drugs and molecules that target VE might serve as good candidates in the treatment of age-related diseases other than CVDs. The findings in SIRT7-based gene therapy implicate great clinical potentials for progeria as well as in antiaging applications.

Lmnaf/+ allele (LmnaG609G mutation flanked by two loxP sites) was generated by Cyagen Biosciences Inc., China. Briefly, the 5 and 3 homology arms were amplified from bacterial artificial chromosome clones RP23-21K15 and RP23-174J9, respectively. The G609G (GGC to GGT) mutation was introduced into exon 11 in the 3 homology arm. C57BL/6 embryonic stem cells were used for gene targeting. To obtain ubiquitous expression of progerin (LmnaG609G/G609G), Lmnaf/f mice were bred with E2A-Cre mice. To obtain VE-specific expression of progerin, Lmnaf/f mice were bred with Tie2-cre mice. Mice were housed and handled in accordance with protocols approved by the Committee on the Use of Live Animals in Teaching and Research of Shenzhen University, China.

Four-month-old male mice were anesthetized with 4% chloral hydrate (0.20 ml/20 g) by intraperitoneal injection. Hindlimb ischemia was performed by unilateral femoral artery ligation and excision, as previously described (41). In brief, the neurovascular pedicle was visualized under a light microscope following a 1-cm incision in the skin of the left hindlimb. Ligations were made in the left femoral artery proximal to the superficial epigastric artery branch and anterior to the saphenous artery. Then, the femoral artery and the attached branches between ligations were excised. The skin was closed using a 4-0 suture line, and erythromycin ointment was applied to prevent wound infection after surgery. Recovery of the blood flow was evaluated before and after surgery using a dynamic microcirculation imaging system (Teksqray, Shenzhen, China). Relative blood flow recovery is expressed as the ischemia-to-nonischemia ratio. At least three mice were included in each experimental group.

HEK293 cells and HUVECs were purchased from the American Type Culture Collection. HEK293 cells were cultured in Gibco Dulbeccos modified Eagles medium (Life Technologies, USA) supplemented with 10% fetal bovine serum at 37C, 5% CO2. HUVECs were cultured in Gibco M199 (Life Technologies, USA) supplemented with 15% fetal bovine serum, EC growth supplement (50 g/ml), and heparin (100 g/ml) at 37C, 5% CO2. All cell lines used were authenticated by short tandem repeat profile analysis and were mycoplasma free.

Total RNA was extracted from cells or mouse tissues using TRIzol reagent RNAiso Plus (Takara, Japan) and transcribed into complementary DNA (cDNA) using 5 PrimeScript RT Master Mix (Takara, Japan), following the manufacturers instructions. The mRNA levels were determined by quantitative PCR with SYBR Premix Ex Taq II (Takara, Japan) detected on a CFX Connect Real-Time PCR Detection System (Bio-Rad). All primer sequences are listed in table S1.

For protein extraction, cells were suspended in SDS lysis buffer and boiled. Then, the lysate was centrifuged at 12,000g for 2 min, and the supernatant was collected. For Western blotting, protein samples were separated on SDS-polyacrylamide gels, transferred to polyvinylidene difluoride membranes (Millipore, USA), blocked with 5% nonfat milk, and incubated with the relevant antibodies. Images were acquired on a Bio-Rad system. All antibodies are listed in table S2.

Frozen sections of aorta, skeletal muscle, and liver tissues were fixed in 4% paraformaldehyde (PFA), permeabilized with 0.3% Triton X-100, blocked with 5% bovine serum albumin and 1% goat serum, and then incubated with primary antibodies at room temperature for 2 hours or at 4C overnight. After three washes with phosphate-buffered saline with Tween 20, the sections were incubated with secondary antibodies for 1 hour at room temperature and then stained with 4,6-diamidino-2-phenylindole antifade mounting medium. Images were captured under a Zeiss LSM 880 confocal microscope. All antibodies are listed in table S2.

Paraffin-embedded sections of PFA-fixed tissues were dewaxed and hydrated. Staining was then performed using a Masson trichrome staining kit (Beyotime, China). In brief, the sections were dipped in Bouin buffer for 2 hours at 37C and then successively stained with Celestine blue staining solution, hematoxylin staining solution, Ponceau S staining solution, and aniline blue solution for 3 min. After dehydrating with ethyl alcohol three times, the sections were mounted with Neutral Balsam Mounting Medium (BBI Life Science, China). Images were captured under a Zeiss LSM 880 confocal microscope.

Mice were euthanized by decapitation. The lungs were then collected, cut into small pieces, and then digested with collagenase I (200 U/ml) and neutral protease (0.565 mg/ml) for 1 hour at 37C. The isolated cells were incubated with phycoerythrin-conjugated anti-CD31 antibody for 1 hour at 4C and then 7-aminoactinomycin D (7-AAD) (1:100) for 5 min. CD31-positive and 7-AADnegative cells were sorted on a flow cytometer (BD Biosciences, USA).

Four-month-old male mice were anesthetized with 4% chloral hydrate by intraperitoneal injection. Thoracic aortas were collected, rinsed in ice-cold Krebs solution, and cut into 2-mm-length rings. Each aorta ring was bathed in 5-ml oxygenated (95% O2 and 5% CO2) Krebs solution at 37C for 30 min in a myograph chamber (620M, Danish Myo Technology). Each ring was stretched in a stepwise fashion to the optimal resting tension (thoracic aortas to ~9 mN) and equilibrated for 30 min. Then, 100 mM K+ Krebs solution was added to the chambers to elicit a reference contraction and then washed out with Krebs solution at 37C until a baseline was achieved. Vasodilation induced by Ach or SNP (1 nM to 100 M) was recorded in 5-hydroxytryptamine (2 M) contracted rings. Data are represented as a percentage of force reduction and the peak of K+-induced contraction. At least three mice were included in each experimental group.

Seven- to 8-month-old male mice were anesthetized by isoflurane gas inhalation and then subjected to transthoracic echocardiography (iU22, Philips). Parameters, including heart rate, cardiac output, left ventricular posterior wall dimension, left ventricular end-diastolic dimension, left ventricular end-systolic diameter, LV ejection fraction, and LV fractional shortening, were acquired. At least three mice were included in each experimental group.

Seven- to 8-month-old male mice were euthanized by decapitation. The thigh bone was fixed in 4% PFA at 4C overnight. The relevant data were collected by micro-CT (Scanco Medical, CT100). At least three mice were included in each experimental group.

A Rota-Rod Treadmill (YLS-4C, Jinan Yiyan Scientific Research Company, China) was used to monitor fatigue resistance. Briefly, mice were placed on the rotating lane, and the speed of the rotations gradually increased to 40 rpm. When the mice were exhausted, they were safely dropped from the rotating lane, and the latency to fall was recorded. At least three mice were included in each experimental group.

CD31+ cells isolated from murine lung by FACS (>90% viability) were used for single-cell RNA sequencing. A sequence library was built according to the Chromium Single-Cell Instrument library protocol (42). Briefly, single-cell RNAs were barcoded and reverse-transcribed using the Chromium Single-Cell 3 Reagent Kits v2 (10 Genomics) and then fragmented and amplified to generate cDNAs. The cDNAs were quantified using an Agilent Bioanalyzer 2100 DNA Chip, and the library was sequenced using an Illumina Hiseq PE150 with ~10 to 30M raw data assigned for each cell. The reads were mapped to the mouse mm9 genome and analyzed using STAR: >90% reads mapped confidently to genomic regions and >50% mapped to exonic regions. Cell Ranger 2.1.0 was used to align reads, generate feature-barcode matrices, and perform clustering and gene expression analysis. Mean reads (>80,000) and 900 median genes per cell were obtained. The unique molecular identifier counts were used to quantify the gene expression levels, and the t-distributed stochastic neighbor embedding (t-SNE) algorithm was used for dimensionality reduction. The cell population was then clustered by k-means clustering (k = 4). The Log2FoldChange was the ratio of gene expression of one cluster to that of all other cells. The P value was calculated using the negative binomial test, and the false discovery rate was determined by the Benjamini-Hochberg procedure. GO and KEGG enrichment analyses were performed in DAVID version 6.8 (43).

A two-tailed Students t test was used to determine statistical significance, except that the statistical comparison of survival data was performed by log-rank test. All data are presented as the means SD or means SEM, as indicated, and a P value <0.05 was considered statistically significant.

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/6/8/eaay5556/DC1

Fig. S1. Generation of Lmnaf/f mice and phenotypic analysis of LmnaG609G/G609G mice.

Fig. S2. Single-cell transcriptomic analysis of CD31+ MLECs.

Fig. S3. VE-specific progerin expression.

Fig. S4. Vasodilation analysis of LmnaG609G/+ mice.

Fig. S5. Expression of atherosclerosis- and osteoporosis-associated genes in MLEC transcriptomes.

Table S1. List of primer sequences.

Table S2. List of antibodies.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: We thank J. Tamanini (Shenzhen University and ETediting) for editing the manuscript before submission. Funding: This study was supported by grants from the National Natural Science Foundation of China (91849208, 81571374, 91439133, 81871114, 81601215, 81972602, and 81702909), the National Key R&D Program of China (2017YFA0503900), the Science and Technology Program of Guangdong Province (2014A030308011, 2017B030301016, and 2019B030301009), and the Shenzhen Municipal Commission of Science and Technology Innovation (JCYJ20160226191451487, KQJSCX20180328093403969, JCYJ20180507182044945, ZDSYS20190902093401689, and Discipline Construction Funding of Shenzhen 2016-1452). Author contributions: B.L. designed and supervised the project. S.S., W.Q., and X.T. conducted experiments with help from W.H., S.Z., M.Q., Z.L., X.C., Q.P., and B.Z. Y.M. performed bioinformatic analysis. Z.W. and Z.Z. provided resources. S.S., X.T., and B.L. wrote the manuscript. All authors discussed the experimental results and reviewed the manuscript. Competing interests: The authors declare that they have no 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. The data of single-cell transcriptomics are available in the GEO database (GSE138975). Additional data related to this paper may be requested from the authors.

Here is the original post:
Vascular endotheliumtargeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model - Science...

Recommendation and review posted by Bethany Smith

Its point-of-care platform advances the development of gene-based medicine through collaborations and in-licensing

Inc () announced a collaboration with Johns Hopkins University to utilize its point-of-care platform to develop and supply gene therapies and technologies.

The companys POCare cell therapy platform is designed to advance the development of Advanced Therapy Medicinal Products medicines based on genes, tissues or cells through collaborations and in-licensing with other companies.

CEO Vered Caplan is confident in the pedigree and resources of the Baltimore research university.

JHU has unparalleled capabilities in the cell and gene therapy sector, Caplan said in a statement. Our POCare platform is designed to provide unique cell and gene therapy solutions in a cost effective, high quality and scalable manner, using closed systems and other advanced cell processing technologies at the point of care.

We look forward to utilizing our POCare platform to support JHUs growing development and processing needs in order to advance and accelerate cell and gene based clinical therapeutic research. We believe this collaboration with JHU, a clear leader in the field of cell and gene therapy, further validates the significant value proposition of our POCare platform.

Johns Hopkins is the third major institution to sign an agreement with , Caplan said. Last month, the company reached a deal with the University of California, Davis.

With its introduction of Orgenesiss POCare platform, hospitals are able to implement the company's proprietary automated, closed systems and know-how to collect, process and supply cells for various treatments such as the manufacturing of CAR-T cell therapies.

The Germantown, Maryland-based company provides centralized contract development and manufacturing organization (CDMO) services, as well as localized point-of-care development and processing centers through its subsidiary Orgenesis Maryland Inc.

Contact Andrew Kessel at [emailprotected]

Follow him on Twitter @andrew_kessel

Continue reading here:
Orgenesis teams up with Johns Hopkins University to develop gene therapies with its POCare platform - Proactive Investors USA & Canada

Recommendation and review posted by Bethany Smith

Audentes Therapeutics, an Astellas company based in San Francisco, California, will open a new facility in Lee County, Governor Roy Cooper announced Tuesday.

The life-sciences company has purchased a recently-completed shell building located in Central Carolina Enterprise Park and will create 209 jobs at an average salary of $83,900. The company will be investing $109.4M in Sanford over a five year period.

With our powerhouse research centers and highly-skilled workforce, biotech pioneers recognize North Carolinas role as a leader in the life sciences, said Governor Cooper. Lee County is a perfect fit for Audentes as they seek to become a global leader in genetic medicines.

Audentes Therapeutics, Inc., an Astellas company, is an AAV-based genetic medicines company focused on developing and commercializing innovative therapies that can offer transformative benefits to patients.

In addition to its gene therapy portfolio targeting serious rare neuromuscular diseases, the company states, Audentes is leveraging Astellas global resources, industry leadership in immune biology, and deep scientific expertise to expand its reach and deliver valuable new genetic medicines to patients around the world.

Lee County Board of Commissioners Chair Amy Dalrymple gave remarks during the announcement, saying, Thank you to Audentes for recognizing the strengths of the Lee County community and for investing in us to create over 200 jobs for Central North Carolina. Lee County looks forward to working together and building a long-term partnership where Audentes and the Lee County community flourishes.

Sanford Mayor Chet Mann stated, We are overjoyed at having Audentes Therapeutics in our community. Their decision to locate here is proof that our Public / Private Partnership and the efforts toward making Sanford a desirable place to live and work have been a success. A company of this quality and the important work they do will have tremendous impact; creating a new Life Sciences cluster that will pay future dividends. We truly look forward to a great partnership with Audentes and we enthusiastically welcome them here.

Sanford Area Growth Alliance Board of Directors Chair Kirk Bradley commented, Its been a little less than 5 years since Mark Sweeney, of the site selection firm, McCallum Sweeney, addressed a group of community and Civic leaders on July 30, 2015 about how Prepared Communities Win.

This message resonated and the announcement of Audentes Therapeutics is the culmination of what can happen to a community that listens to experts and harnesses private and public capital for a common objective of economic growth.

Today Sanford, Broadway and Lee County has one of the most, if not THE most, thriving economic development eco-system in the State of North Carolina. We are honored that Governor Cooper would make this historic announcement. We welcome Audentes Therapeutics to our community as a new corporate citizen with open arms for a successful future!

Contributed

Continue reading here:
Leading gene therapy company to invest $109M in Sanford - Sandhill Sentinel

Recommendation and review posted by Bethany Smith

Dive Brief:

Bluebird's commercial operations are just getting off the ground. In its latest earnings report, the Cambridge, Massachusetts-based biotech detailed how it has inked agreements with health insurers in Germany that should provide coverage for LentiGlobin, which is sold under the brand name Zyntegloin Europe, for up to 50% of eligible beta-thalassemia patients. Bluebird expects the first commercial patient to be treated before July.

Across the Atlantic, U.S. patients are looking at a longer timeline before LentiGlobin becomes available. Stifel analysts wrote in a note to clients that they don't foresee any stateside patients receiving the therapy commercially in 2020 "given what we anticipate will be a complicated negotiation process with payors."

Analysts at Raymond James, meanwhile, downgraded Bluebird to a "Market Perform" rating, writing that "execution issues on the regulatory, clinical and manufacturing side outweigh our support for the innovative drug products."

As Bluebird works through the latest delay in beta-thalassemia,it will also be preparing for an expanded research program in sickle cell. The company already intended to kick off a late-stage study in sickle cell patients with a history of vaso-occlusive crises in the first half of 2020. With Tuesday's earnings presentation, though, came plans to initiate a second late-stage study sometime this year, which will evaluate LentiGlobin's effects in about 18 children with sickle cell and elevated stroke risk.

A sickle cell approval, though a ways off, could boost Bluebird's bottom line. Beta-thalassemiais rarer in U.S. than other parts of the world, and certainly less common than sickle cell. According to estimates cited by the National Organization of Rare Disorders, roughly 3,300 U.S. patients have beta-thalassemiaversus the 100,000 who have sickle cell.

An expanded program could provide more evidence of LentiGlobin's benefit in this larger patient pool.Yet the updates don't seem to have alleviated investor concerns. Bluebird shares were down nearly 10% in late Wednesday morning, trading around $80 apiece.

"LentiGlobin in Sickle Cell Disease remains a bright spot, in our view, but with [late-stage studies] expected to get underway this year, we don't expect investor sentiment to change anytime soon," Stifel analysts wrote.

The investment bank models Zyntelgo bringing in $12 million worth of revenue in 2020 from the beta-thalassemia indication, increasing to $53 million in 2021 and $390 million by 2030. Conversely, it models $48 million in 2022 from the sickle cell indication, increasing to almost $2 billion by 2030.

Read the original here:
Bluebird's gene therapy hits another delay, this time in the US - BioPharma Dive

Recommendation and review posted by Bethany Smith

The vaccine and cell and gene therapy biomanufacturing sectors are growing at an accelerated rate with the US and Europe driving a significant segment of this growth. European biopharma and CDMO scientists often ask if we have representation in the region as they search for innovative tools to alleviate their production and QC bottlenecks; we can now finally say yes to this important question," says Dr. Sean Hart, LumaCytes Chief Executive Officer. In support of these efforts, LumaCyte has hired analytical instrumentation veteran, Christof Hasse, PhD to manage sales and service as part of its European expansion. At LumaCyte, were obsessed with delivering exceptional customer service, so having Laser Force Cytology (LFC) experts who understand our customers unique needs, and are located in the same region, is critical to delivering the highest level of service, says Rene Hart, LumaCyte President and Chief Business Officer. We are excited to have Christof on board as he brings LumaCytes transformative Laser Force Cytology to the hands of European researchers and production scientists.

About LumaCyte

LumaCyte is an advanced research and bioanalytics instrumentation company headquartered in Charlottesville, VA. LumaCyte produces label-free, single cell analysis and sorting instrumentation where the use of antibody or genetic labeling is not required for cellular analysis. This revolutionary technology utilizes Laser Force Cytology (LFC) to measure optical and fluidic forces within a microfluidic channel to identify and measure the intrinsic cellular properties of each cell. The multivariate nature of the data has enabled a host of Big Data strategies and cloud computing capabilities that drive advanced analytics, allowing a deeper understanding of cell based biological systems. Applications of LumaCyte's label-free platform technology include viral infectivity for vaccine development and manufacturing, cell and gene therapy, cancer biology R&D, CAR T cell immunotherapy, adventitious agent testing (AAT), iPSCs, infectious disease, and pre-clinical drug discovery, in addition to multiple applications across the biomanufacturing sector for quality control and process optimization.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200220005263/en/

Excerpt from:
LumaCyte Expands into Europe Tackling Expansive Vaccine and Cell and Gene Therapy Markets - BioSpace

Recommendation and review posted by Bethany Smith

With more and more cell therapies entering the market, Dr Maitry Ganatra, global market development director at Thermo Fisher Scientific guides readers on how to comply with regulatory standards to ensure quality and safety, and ultimately make it to commercialisation.

In recent years, sophisticated cell therapies have emerged to treat a broad range of cardiovascular, neurological and autoimmune diseases, among others. The complexity and variability of these therapies present unique challenges for the transition from the research phase to commercialisation. Thorough consideration of current good manufacturing practice (cGMP) requirements and regulatory compliance early in the process, even during the research stage, can help alleviate the challenges involved in scaling up. Additionally, applying quality by design (QbD) principles to the production process can ensure high quality and safety of new therapeutics, making commercialisation easier.

Commercialisation of cell and gene therapies, whether allogeneic or autologous, can be challenging. In allogeneic cell therapy, where a single cell type is mass produced for treating multiple patients, the challenge is that of scaling up a thousand-fold from the research phase, while still maintaining the necessary physiological conditions. When processes get scaled up, laboratory instruments, such as centrifuges and CO2 incubators used during the research phase, may not be compatible with the requirements of the cGMP environment. Typically, when equipment designed for research purposes are used in a cGMP compliant facility without consideration of validation and documentation requirements, this can pose a huge issue during commercialisation.

Scaling up could introduce inconsistencies across multiple factors, including incubator temperature, composition of reagents, such as media or growth factors, as well as cell culture parameters, such as incubation time. Even the slightest change in production conditions upon moving from research level to the multi-liter scale can have an impact on how the cells behave, ultimately affecting the quality and safety of the therapy. In adapting research workflows to meet commercial cGMP requirements, cell therapy manufacturers often realise too late that processes that work well at the research stage are incompatible with the cGMP environment. Furthermore, they often underestimate how involved the regulatory compliance process can be; each piece of equipment needs to be validated to ensure it meets the highest standards and relevant documentation should be produced.

In autologous cell therapy, where each batch of cells is produced for only one patient, modified and re-introduced into the same patient, the challenge is that of scaling out and producing multiple batches corresponding to multiple patients, while maintaining due diligence throughout the process-heavy workflow.

Scaling out in autologous cell therapy demands more space and a large number of instruments, each being compliant with regulatory standards. The challenges here involve managing the complexity of working with multiple sets of equipment, having sufficient space for all these systems and keeping track of which instrument is used for a specific therapy. When processing multiple batches in autologous cell therapy, every patient sample needs to be tracked as it goes from the hospital to the manufacturing site and back to the patient, thereby adding logistical burden to the process. On the whole, scaling out relies on having the operational capacity to accommodate all the equipment as well as the materials, manpower and time involved in the process.

Recognising these challenges, many technology vendors offer advice and guidance around cGMP compatible instrumentation, including centrifuges, biological safety cabinets, cold storage equipment and CO2 incubators. A standard laboratory CO2 incubator, for example, cannot be moved to a cGMP environment without temperature mapping or testing for installation, operational and performance qualifications (IQ, OQ and PQ). To this effect, some vendors even offer customisable solutions to help meet cGMP requirements.

Applying quality by design principles to cell therapy manufacturing

Increased testing does not necessarily improve the quality of the final product. A more robust solution is to build quality into entire production workflows. The US Food and Drug Administration (FDA) encourages implementation of the Quality by Design (QbD) principles into the production, manufacturing and regulation processes.

In adopting the QbD principles, every step of the process, starting from raw materials to the operating plant, clean room, and water and materials used, all should adhere to high-quality standards. Every piece of equipment used in the manufacturing process needs to meet quality requirements, such as being certified by the International Organisation for Standardisation.

Recognising the challenges posed when transitioning from research to commercialisation of cell and gene therapies, many instrument vendors apply the QbD principles and undertake all of the necessary performance testing to deliver equipment that meet the requirements of cGMP compliant facilities. Some of the steps involved in performance testing include temperature testing, ramp up/ramp down testing, sterilisation, and electrical checks. By inspecting the overall safety and configuration of the instrumentation, the required factory end-of-line testing is completed.

Vendors also provide the relevant documentation required in adhering with the cGMP standards, for example, issuing the certificate of conformance and providing instrument calibration documentation, equipment drawing and critical component specifications. To ensure that each piece of equipment is installed per vendor specifications, meets the quality requirements, and offers consistent and reproducible results, IQ, OQ and PQ validation protocols are performed, followed by issuing the respective documentation.

In addition to testing for compliance and offering documentation, some vendors provide user and maintenance training to ensure best practices are upheld in the day-to-day workflow.

As pharmaceutical manufacturers transition cell therapies from the research to the commercialisation phase, they start acknowledging the complexity that comes from scaling up and expanding workflows, while staying compliant with the regulatory requirements. Carefully planning cell therapy production processes beforehand, understanding the needs of cGMP compliance and collaborating with knowledgeable technology vendors who offer solutions adhering to QbD principles, can set cell therapy manufacturers up for successful commercialisation.

See the original post:
Getting cell therapies to market - EPM Magazine

Recommendation and review posted by Bethany Smith

- First conditional approval of ZYNTEGLOTM (autologous CD34+ cells encoding A-T87Q-globin gene) gene therapy for patients 12 years and older with transfusion-dependent -thalassemia who do not have 0/0 genotype in Europe achieved in 2019; Germany launch underway

- Announced positive top-line data from pivotal Phase 2 KarMMa study of ide-cel in relapsed and refractory multiple myeloma

- Presented clinical data across studies of LentiGlobin gene therapy for -thalassemia (betibeglogene autotemcel) and LentiGlobin gene therapy for sickle cell disease (SCD) and bb21217 in multiple myeloma at American Society of Hematology (ASH) Annual Meeting

- Ended quarter with $1.24 billion in cash, cash equivalents and marketable securities

bluebird bio, Inc. (NASDAQ: BLUE) today reported financial results and business highlights for the fourth quarter and full year ended December 31, 2019.

"2019 was truly a transformative year for bluebird, with our first commercial product now launched in Europe and exciting progress across our first four clinical programs and pipeline," said Nick Leschly, chief bluebird. "Notably, our data in SCD continues to build, and at the ASH annual meeting in December we presented data that showed a 99% reduction in the annualized rate of vaso-occlusive crises (VOC) and acute chest syndrome (ACS) in HGB-206 Group C patients with history of VOCs and ACS who had at least six months follow-up. In -thalassemia, the consistency with which patients who do not have a 0/0 genotype in our Northstar-2 (HGB-207) study are achieving transfusion independence is very encouraging and were starting to see indications that we may be able to see similar outcomes with many patients with 0/0 genotypes as well in our Northstar-3 (HGB-212 study). These data put us in a strong position as we progress our European launch, currently underway in Germany. At the end of 2019, we also announced positive top-line data from the pivotal KarMMa study of ide-cel. We and our partners at BMS look forward to submitting these data to the FDA in the first half of this year. Amidst all of our progress in 2019, our birds demonstrated time and again their dedication to patients and ability to meet and learn from the many challenges we have faced along the way. I look forward to facing the challenges of 2020 with this amazing flock."

Recent Highlights:

TRANSFUSION-DEPENDENT -THALASSEMIA

SICKLE CELL DISEASE (SCD)

MULTIPLE MYELOMA

COMPANY

Upcoming Anticipated Milestones:

Fourth Quarter and Full Year 2019 Financial Results

LentiGlobin for -thalassemia Safety

Non-serious adverse events (AEs) observed during the HGB-204, HGB-207 and HGB-212 clinical studies that were attributed to LentiGlobin for -thalassemia were hot flush, dyspnoea, abdominal pain, pain in extremities, thrombocytopenia, leukopenia, neutropenia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to LentiGlobin for -thalassemia for TDT.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

With more than five years of follow-up to date, there have been no new unexpected safety events, no deaths, no graft failure and no cases of vector-mediated replication competent lentivirus or clonal dominance. In addition, there have been no new reports of veno-occlusive liver disease (VOD) as of the data cutoff presented at ASH.

About LentiGlobin for -Thalassemia (betibeglogene autotemcel)

The European Commission granted conditional marketing authorization for LentiGlobin for -thalassemia, to be marketed as ZYNTEGLO (autologous CD34+ cells encoding A-T87Q-globin gene) gene therapy, for patients 12 years and older with TDT who do not have a 0/0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

TDT is a severe genetic disease caused by mutations in the -globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Story continues

LentiGlobin for -thalassemia adds functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

The conditional marketing authorization for ZYNTEGLO is only valid in the 28 member states of the EU as well as Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. Food and Drug Administration granted LentiGlobin for -thalassemia Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.

bluebird bio has initiated its rolling BLA submission of LentiGlobin for -thalassemia for approval in the U.S. and is engaged with the FDA in discussions regarding the requirements and timing of certain information to be provided in the BLA, including information regarding various release assays for LentiGlobin for -thalassemia. Subject to these ongoing discussions, the company is currently planning to complete the BLA submission in the second half of 2020.

LentiGlobin for -thalassemia continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit http://www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207), NCT03207009 for Northstar-3 (HGB-212).

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for -thalassemia. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

ZYNTEGLO, LentiGlobin, and bluebird bio are trademarks of bluebird bio, Inc.

The full common name for ZYNTEGLO: A genetically modified autologous CD34+ cell enriched population that contains hematopoietic stem cells transduced with lentiviral vector encoding the A-T87Q-globin gene.

Forward-Looking Statements

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the companys financial condition, results of operations, as well as statements regarding the plans for regulatory submissions and commercialization for ZYNTEGLO and the companys product candidates, including anticipated regulatory milestones, the execution of the companys commercial launch plans, planned clinical studies, as well as the companys intentions regarding the timing for providing further updates on the development and commercialization of ZYNTEGLO and the companys product candidates. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated in our ongoing or future clinical trials; the risk of cessation or delay of any of the ongoing or planned clinical studies and/or our development of our product candidates; the risk that the current or planned clinical trials of our product candidates will be insufficient to support regulatory submissions or marketing approval in the United States and European Union; the risk that regulatory authorities will require additional information regarding our product candidates, resulting in delay to our anticipated timelines for regulatory submissions, including our applications for marketing approval; the risk that we will encounter challenges in the commercial launch of ZYNTEGLO in the European Union, including in managing our complex supply chain for the delivery of drug product, in the adoption of value-based payment models, or in obtaining sufficient coverage or reimbursement for our products; the risk that our collaborations, including the collaborations with Bristol-Myers Squibb and Forty Seven, will not continue or will not be successful; and the risk that any one or more of our product candidates, will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

bluebird bio, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except per share data)(unaudited)

For the three months endedDecember 31,

For the year endedDecember 31,

2019

2018

2019

2018

Revenue:

Collaboration revenue

$ 7,159

$ 18,382

$ 36,469

$ 52,353

License and royalty revenue

2,838

861

8,205

2,226

Total revenues

9,997

19,243

44,674

54,579

Operating expenses:

Research and development

161,821

119,722

582,413

448,589

Selling, general and administrative

76,202

53,508

271,362

174,129

Cost of license and royalty revenue

1,073

818

2,978

885

Change in fair value of contingent consideration

1,435

2,156

2,747

2,999

Total operating expenses

240,531

176,204

859,500

626,602

Loss from operations

(230,534)

(156,961)

(814,826)

(572,023)

Interest income, net

6,855

6,209

34,761

14,624

Other (expense) income, net

535

1,916

(10,088)

1,961

Visit link:
bluebird bio Reports Fourth Quarter and Full Year 2019 Financial Results and Highlights Operational Progress - Yahoo Finance

Recommendation and review posted by Bethany Smith

Studies by researchers at University of South Florida Health (USF Health) Morsani College of Medicine have found that a protein known as -arrestin2 increases the accumulation of the neurotoxic tau tangles that cause several forms of dementia, by interfering with the process that cells use to remove excess tau from the brain. The studies demonstrated that an oligomerized form of -arrestin2, but not monomeric -arrestin2, disrupted the process of autophagy, which would normally act to help rid cells of malformed proteins like disease-causing tau.

Encouragingly, in vivo studies showed that blocking -arrestin2 oligomerization suppressed disease-causing tau in a mouse model that develops a form of human frontotemporal lobar degeneration (FTLD) with dementia, a form of neurodegeneration that is characterized by tau accumulation and the formation of neurofibrillary tangles. Our research could lead to a new strategy to block tau pathology in FTLD, Alzheimers disease, and other related dementias, which ultimately destroys cognitive abilities such as reasoning, behavior, language, and memory, said Jung-A (Alexa) Woo, PhD, an assistant professor of molecular pharmacology and physiology and an investigator at the USF Health Byrd Alzheimers Center. Woo is lead author of the teams published paper in theProceedings of the National Academy of Sciences(PNAS), which is titled, -arrestin2 oligomers impair the clearance of pathological tau and increase tau aggregates.

FTLD, which is also called frontotemporal dementia, is second only to Alzheimers disease (AD) as the leading cause of dementia. This aggressive form of dementia is typically earlier onset, in people aged 4565, and is characterized by atrophy of the front or side regions of the brain, or both. The two primary hallmarks of Alzheimers disease are clumps of amyloid-beta (A) protein fragments known as amyloid plaques, and the tangles of tau protein. Abnormal accumulations of both proteins are needed to drive the death neurons in Alzheimers, although recent research suggests that tau accumulation appears to be required for the toxic effects of A in AD, and correlates better with cognitive dysfunction than A. Indeed, tauopathy correlates significantly better than A with cognitive deficits in AD, the team noted, and drugs targeting A have been disappointing as a treatment.

Like Alzheimers disease, FTLD displays an accumulation of tau, which results in the formation of tau-laden neurofibrillary tangles that destroy synaptic communication between neurons, eventually killing the brain cells. There is no specific treatment or cure for FTLD. However, in contrast with AD, A aggregation is absent in the FTLD brain, in which the key feature of neurodegeneration appears to be the excessive tau accumulation, known as tauopathy. In contrast to AD, where amyloid is an integral part of the tangle, there is no accumulation of A in FTLD neurons , the authors noted.

Previous studies have pointed to an association between G protein-coupled receptors (GPCRs) and AD pathogenesis, and have linked the activation of several, diverse GPCRs with A and/or tau pathogenesis in animal models. While it isnt clear how these very different GPCRs can impact on A and tau pathogenesis, and neurodegeneration in AD, one potential commonality among the receptors is their interaction with arrestins, the researchers noted. Interestingly, previous studies have shown that one of the family of -arrestin proteins known as -arrestin2, is increased in AD brains, and genetic studies have shown that endogenous -arrestin2 promotes A production and deposition, linking -arrestin2 to A pathogenesis. Despite this evidence, the authors acknowledged, prior to the current work, however, it was not known whether, or how, -arrestin2 pathogenically impinges on tauopathy and neurodegeneration in AD, or in FTLD where there is no accumulation of A. As Woo commented, Studying FTLD gave us that window to study a key feature of both types of dementias, without the confusion of any A component.

-arrestin2 in its monomeric form is mostly known for its ability to regulate receptors, but -arrestin2 can also form multiple interconnecting units, called oligomers, and the function of -arrestin2 oligomers is not well understood. While the monomeric form was the basis for the laboratorys initial studies examining tau and its relationship with neurotransmission and receptors, Woo said, we soon became transfixed on these oligomers of -arrestin2.

The teams studies confirmed the presence of elevated -arrestin2 levels, both in cells from the brains of TFLD-tau patients, and in a mouse model. This model expresses disease-associated tau in neurons, and displays FTLD-like pathophysiology and behavior and, like FTLD in humans, doesnt accumulate A.

The researchers also found that -arrestin2 acts to increase tau stability via scaffolding potein:protein interactions. Their results indicated that when -arrestin2 is overexpressed, tau levels also increase, suggesting a maladaptive feedback cycle that exacerbates disease-causing tau. As the authors commented, the data suggested that increased tau increases -arrestin2, which in turn acts to further potentiate tau-mediated events by stabilizing the protein, thus indicative of a vicious positive pathogenic feedback cycle.

To determine the effects of reducing -arrestin2 levels, the team crossed a mouse model of early tauopathy with genetically modified mice in which the -arrestin2 gene was inactivated. They demonstrated that genetic knockdown of -arrestin2 also reduced tauopathy, synaptic dysfunction, and the loss of nerve cells and their connections in the brain. Importantly, experiments confirmed that it was oligomerized -arrestin2, and not the proteins monomeric form, which was associated with increased tau. By blocking -arrestin2 molecules from binding together to create oligomerized forms of the protein, the investigators demonstrated that pathogenic tau significantly decreased when only monomeric -arrestin2, which does bind to receptors, was present.

Further experiments indicated that oligomerized -arrestin2 increases tau by impeding the ability of cargo protein p62 to help selectively degrade excess tau in the brain. In effect, this reduces the efficiency of the autophagy process that would otherwise clear toxic tau. The resulting accumulation of tau clogs up the neurons. Blocking -arrestin2 oligomerization also suppressed disease-causing tau in the mouse model that develops human tauopathy with signs of dementia.

Specifically, our results indicate that -arrestin2 oligomers increase tau levels by blocking the self-interaction of p62, an initial step essential in p62-mediated autophagy flux, the team commented. Genetic reduction or ablation of -arrestin2 significantly decreased sarkosyl-insoluble tau and mitigated tauopathy in vivo. Furthermore, -arrestin2 mutants incapable of forming oligomersactually reduced insoluble tau.

It has always been puzzling why the brain cannot clear accumulating tau, said Stephen B. Liggett, MD, senior author and professor of medicine and medical engineering at the USF Health Morsani College of Medicine. It appears that an incidental interaction between -arrestin2 and the tau clearance mechanism occurs, leading to these dementias. -arrestin2 itself is not harmful, but this unanticipated interplay appears to be the basis for this mystery We also noted that decreasing -arrestin2 by gene therapy had no apparent side effects, but such a reduction was enough to open the tau clearance mechanism to full throttle, erasing the tau tangles like an eraser. This is something the field has been looking foran intervention that does no harm and reverses the disease.

The results point to a potential therapeutic strategy for tauopathies such as FTLD, based on partial inhibition of -arrestin2 oligomerization. For gene therapy of human FTLD-tau, mutants with a somewhat decreased capacity for such inhibition might be desirable, so that some levels of the oligomer are present to carry out other functions Similarly, small molecule inhibitors of -arrestin2 oligomerization, given for treatment or prevention of FTLD-tau, could be designed to spare complete loss of the oligomer in the cell, they suggested. Based on our findings, the effects of inhibiting -arrestin2 oligomerization would be expected to not only inhibit the development of new tau tangles, but also to clear existing tau accumulations due to this mechanism of enhancing tau clearance.

This treatment strategy could be both preventative for at-risk individuals and those with only mild cognitive impairment, and therapeutic in patients with evident FTLD-tau, by decreasing existing tau tangles. Beyond tauopathy, it is conceivable that this strategy could also prove to be beneficial in other neurodegenerative diseases bearing proteinopathies that are cleared via p62, the scientists concluded.

This study identifies beta-arrestin2 as a key culprit in the progressive accumulation of tau in brains of dementia patients, added co-author David Kang, PhD, professor of molecular medicine and director of basic research for the Byrd Alzheimers Center. It also clearly illustrates an innovative proof-of-concept strategy to therapeutically reduce pathological tau by specifically targeting beta-arrestin oligomerization.

View original post here:
Protein that Prevents Tau Clearance Linked to AD and Other Tau Tangle Proteinopathies - Clinical OMICs News

Recommendation and review posted by Bethany Smith

The Global Gene Therapy Market is expected to grow from USD 1,636.49 Million in 2018 to USD 6,436.64 Million by the end of 2025 at a Compound Annual Growth Rate (CAGR) of 21.60%.

The Gene Therapy Market research presents a study by combining primary as well as secondary research. The report gives insights on the key factors concerned with generating and limiting Gene Therapy market growth.

Additionally, the report also studies competitive developments, such as mergers and acquisitions, new partnerships, new contracts, and new product developments in the global Gene Therapy market. The past trends and future prospects included in this report makes it highly comprehensible for the analysis of the market. Moreover, the latest trends, product portfolio, demographics, geographical segmentation, and regulatory framework of the Gene Therapy market have also been included in the study.

Request a Sample Copy of the Report https://www.regalintelligence.com/request-sample/24119

Gene Therapy Market Segment by Manufacturers includes: Achieve Life Sciences, Inc., Adaptimmune, Bluebird bio, Inc., Gilead, Merck & Co., Inc, Abeona Therapeutics, Inc.,, AGTC, Audentes Therapeutics, Biogen, Editas Medicine, Novartis, Orchard Therapeutics, and Spark Therapeutics.

On the basis of Type, the Global Gene Therapy Market is studied across Antigen Gene Therapy, Cancer Gene Therapy, Cytokine Gene Therapy, Suicide Gene Therapy, and Tumor Suppressor Gene Therapy.

On the basis of Vector Type, the Global Gene Therapy Market is studied across Non-viral Vectors and Viral Vectors.

On the basis of Application, the Global Gene Therapy Market is studied across Cardiovascular Diseases, Genetic Diseases, Infectious Diseases, Neurological Diseases, and Oncological Disorders.

Global Gene Therapy market report covers all the major participants and the retailers will be in conscious of the development factors, market barriers & threats, and the opportunities that the market will offer in the near future. The report also features the historical revenue of the market; industry trends, market volume, and consumption in order to gain perceptions about the political and technical environment of the Gene Therapy market share.

This report focuses on the Gene Therapy in Global market, especially in

Enquire or share your questions if any before the purchasing this report https://www.regalintelligence.com/enquiry/24119

The report gives detailed analysis in terms of qualitative and quantitative data pertaining to the projected potential opportunities that influence markets growth for the forecast period. With a major focus on the key elements and segments of the global Gene Therapy market that might affect the growth prospects of the market, making it a highly informative document.

Major Points covered in this Report:

Market Segmentation:

Regional market analysis

The content of the study subjects includes a total of 15 chapters:

Ask For Table of Contents: https://www.regalintelligence.com/request-toc/24119

About Us:We, Regal Intelligence, aim to change the dynamics of market research backed by quality data. Our analysts validate data with exclusive qualitative and analytics driven intelligence. We meticulously plan our research process and execute in order to explore the potential market for getting insightful details. Our prime focus is to provide reliable data based on public surveys using data analytics techniques. If you have come here, you might be interested in highly reliable data driven market insights for your product/service,reach us here 24/7.

Contact Us:Regal Intelligencewww.regalintelligence.comsales@regalintelligence.comPh no: +1 231 930 2779 (U.S.)

Follow Us:https://in.linkedin.com/company/regal-intelligencehttps://www.facebook.com/regalintelligence/https://twitter.com/RI_insights

See more here:
Gene Therapy Market to Witness Considerable Growth Owing to Extensive Demand & Rise in Industrialization by 2025 - Galus Australis

Recommendation and review posted by Bethany Smith

TEL AVIV, Israel, Feb. 20, 2020 (GLOBE NEWSWIRE) -- VBL Therapeutics (Nasdaq: VBLT) today announced the launch of a phase 2 clinical trial of VB-111 in combination with nivolumab (Opdivo), an immune checkpoint inhibitor, in the treatment of metastatic colorectal cancer. The National Cancer Institute (NCI) will serve as the Investigational New Drug (IND) sponsor for this study and the IND application has been approved by the U.S. Food and Drug Administration (FDA). This new study will investigate if priming with VB-111 can drive immune cells into the tumor and turn the colorectal tumor from immunologically cold to hot. The addition of nivolumab to VB-111 may further boost the anti-tumor immune response.

This phase 2 study is part of our strategy to broaden the potential indications for VB-111 and to explore its activity as part of combination therapies, said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics. We look forward to collaborating with NCI on this clinical trial, as we continue to generate data which adds to our understanding of VB-111s mechanism of action and therapeutic potential. We were particularly encouraged by results in ovarian cancer demonstrating the recruitment of infiltrating T cells into a tumor following treatment with VB-111, turning the tumor hot. This important finding suggests that VB-111 may be applied to other cold tumors, in which checkpoint inhibitors show limited or no efficacy, including colorectal cancer, for which there remains a major unmet need.

VBL and the NCI have entered into a Cooperative Research and Development Agreement (CRADA) under the direction of Tim F. Greten, M.D., Deputy Branch Chief & Senior Investigator of the Thoracic and GI Malignancies Branch (TGMB) and Co-Director of the NCI Center for Cancer Research (CCR) Liver Cancer Program. The goal of this open-label, single-arm phase 2 study is to evaluate VB-111 in combination with an anti-PD-1 inhibitor, nivolumab, in patients with metastatic colorectal cancer. In addition to safety and tolerability, this study will evaluate efficacy endpoints including Best Overall Response, as well as immunological and histologic readouts from tumor biopsies. For additional information refer to https://clinicaltrials.gov/show/NCT04166383.

For patients interested in enrolling in this clinical study, please contact NCIs toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the Web site: https://trials.cancer.gov

About VBLVascular Biogenics Ltd., operating as VBL Therapeutics, is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class treatments for cancer. VBLs lead oncology product candidate, ofranergene obadenovec (VB-111), is a first-in-class, targeted anti-cancer gene-therapy agent that is being developed to treat a wide range of solid tumors. It is conveniently administered as an IV infusion once every two months. It has been observed to be well-tolerated in >300 cancer patients and demonstrated activity signals in a VBL-sponsored all comers phase 1 trial as well as in three VBL-sponsored tumor-specific phase 2 studies. Ofranergene obadenovec is currently being studied in a VBL-sponsored phase 3 potential registration trial for platinum-resistant ovarian cancer.

Forward Looking StatementsThis press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as anticipate, believe, could, estimate, expect, goal, intend, look forward to, may, plan, potential, predict, project, should, will, would and similar expressions. These forward-looking statements include, but are not limited to, statements regarding our programs, including VB-111, including their clinical development, such as the timing of clinical trials and expected announcement of data, therapeutic potential and clinical results, and our financial position and cash runway. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, the risk that historical clinical trial results may not be predictive of future trial results, that our financial resources do not last for as long as anticipated, and that we may not realize the expected benefits of our intellectual property protection. A further list and description of these risks, uncertainties and other risks can be found in our regulatory filings with the U.S. Securities and Exchange Commission, including in our annual report on Form 20-F for the year ended December 31, 2018, and subsequent filings with the SEC. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. VBL Therapeutics undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

INVESTOR CONTACT:

Michael RiceLifeSci Advisorsmrice@lifesciadvisors.com(646) 597-6979

See the original post here:
VBL Therapeutics Announces the Launch of a New Clinical Trial of VB-111 Combined with the Checkpoint Inhibitor, Nivolumab, in Metastatic Colorectal...

Recommendation and review posted by Bethany Smith

Viral Vector and Plasmid DNA Manufacturing Market

Facts and Factors Market Researchhas published a new report titled Viral Vector and Plasmid DNA Manufacturing Market By Product (Viral Vectors and Plasmid), By End-User (Biopharmaceutical Companies and Research Institutes), and By Application (Gene & Cancer Therapies, Formulation Development, Viral Infections, and Immunotherapy): Global Industry Perspective, Comprehensive Analysis, and Forecast, 2018 2027. According to the report, the globalviral vector and plasmid DNA manufacturing marketwas valued at approximately USD 418 million in 2018 and is expected to reach a value of around USD 2,237 million by 2027, at a CAGR of around 20.5 % between 2019 and 2027.

Viral vectors are altered viruses that are utilized for inserting genetic material into a cell that can be manipulated for the purpose of healing. These viral vectors prevent the new gene from getting degraded through the delivery of gene castle in the targeted cell. The latter makes use of the new gene to carry out its function. Various kinds of viral vectors include adenoviruses, lentiviruses, and adeno-associated viruses.

Request Free Sample Copy of Research Report @ https://www.fnfresearch.com/sample/viral-vector-and-plasmid-dna-manufacturing-market-by-163

(The sample of this report is readily available on request).

This Free report sample includes:

Plasmid DNA gene is utilized for the purpose of cloning, transferring, and manipulating the gene. The key qualities of plasmid include easy working with self-replicating and stability. They are mainly utilized for understanding the gene function and examining RNAs and other genetic material. Plasmid DNA is sectored into conjugative plasmids and non-conjugative plasmids.

Growing occurrence of chronic ailments to drive the market trends

A prominent rise in the aging population prone to chronic disorders along with an increase in incidences of chronic diseases is likely to upsurge the growth of viral vector and plasmid DNA manufacturing industry over the forecast timeline. Moreover, gene therapy offers major treatment facilities for chronic ailments like cancer, inherited diseases, and viral infections.

Inquire more about this report before purchase @https://www.fnfresearch.com/inquiry/viral-vector-and-plasmid-dna-manufacturing-market-by-163

(You may enquire a report quote OR available discount offers to our sales team before purchase).

Furthermore, the rise in the allocation of funds by private firms on research activities is predicted to drive the market expansion over the forecast timespan. Apart from this, manufacturers are implementing new techniques such as cell line culture development, expression systems, and cell culture system for effectively handling activities related to viral-based vector development. All these factors will upsurge market growth during the forecast period. Nonetheless, the risk of mutagenesis & other obstructions in gene therapy as well as huge costs associated with gene treatment will put brakes on the growth of the market over the forecast period.

Gene & Cancer therapies segment to dominate the application landscape over the forecast period

The growth of the segment is attributed to the rise in the number of gene & cancer therapy subjects along with rapid clinical growth. Apart from this, viral vectors are used for developing gene and T-cell therapies and this will further steer the segmental growth.

Research Institutes to contribute majorly towards the overall market revenue by 2027

The growth of the research institutes segment is attributed to the rise in the research & development activities for launching new therapies to treat chronic ailments like cancer.

North America to dominate the overall regional market growth in terms of revenue by 2027

The growth of the market in the region over the forecast period is due to large-scale government assistance for carrying research activities along with the presence of biopharmaceutical firms in North America. The U.S. is likely to be the regional revenue driver during the forecast timeline.

Request Customized Copy of Report @https://www.fnfresearch.com/customization/viral-vector-and-plasmid-dna-manufacturing-market-by-163

(We customize your report according to your research need. Ask our sales team for report customization).

Some of the key players in the viral vector and plasmid DNA manufacturing business include Kaneka Corporation (Eurogentec), Cobra Biologics, VGXI, Inc., DNA manufacturing market include Lonza, FUJIFILM Diosynth Biotechnologies Inc., Genzyme Corporation, Vigene Biosciences Inc., Brammer Bio, Oxford Gene Technology, SIRION Biotech GmbH, FinVector Vision Therapies, VIROVEK, Novasep, SPARK THERAPEUTICS, INC., ALDEVRON, and General Electric Company (GE Healthcare).

This report segments the viral vector and plasmid DNA manufacturing market as follows:

Global Viral Vector and Plasmid DNA ManufacturingMarket: By Product Segment Analysis

Global Viral Vector and Plasmid DNA ManufacturingMarket: By End-User Segment Analysis

Global Viral Vector and Plasmid DNA ManufacturingMarket: ByApplicationSegment Analysis

GlobalViral Vector and Plasmid DNA ManufacturingMarket: Regional Segment Analysis

About Us:

Facts & Factors is a leading market research organization offering industry expertise and scrupulous consulting services to clients for their business development. The reports and services offered by Facts and Factors are used by prestigious academic institutions, start-ups, and companies globally to measure and understand the changing international and regional business backgrounds. Our clients/customers conviction on our solutions and services has pushed us in delivering always the best. Our advanced research solutions have helped them in appropriate decision-making and guidance for strategies to expand their business.

Contact Us:

Facts & Factors

Global Headquarters

Level 8, International Finance Center, Tower 2,8 Century Avenue, Shanghai,Postal 200120, ChinaTel: +86 21 80360450

Email:sales@fnfresearch.com

Web:https://www.fnfresearch.com

Sorry! The Author has not filled his profile.

See more here:
Global Viral Vector and Plasmid DNA Manufacturing Market to be Worth $2,237 Million by 2027 | CAGR 20.50% - Global Newspaper 24

Recommendation and review posted by Bethany Smith

A PHOTOGRAPHY exhibition showcasing ground-breaking NHS research taking place across the Thames Valley has been launched in Oxford.

TitledThe Body Unlocked: How Research is Changing Lives, it features life-sized photographs of people who have taken part in studies, researchers at work and microscopic images of cells and bacteria.

Images include surgeons preparing a pioneering gene therapy injection for vision loss, dogs smelling urine to detect cancer, a close-up of cells responsible for controlling blood sugar and a virtual reality headset to treat mental illnesses.

The exhibition can be seen for the next two months at Oxfords Covered Market, in the windows of a unit opposite Wicked Chocolate.

ALSO READ: Scientists working on a coronavirus vaccine in Oxford

Among those featured in the exhibition are dementia study participants Barry and Enid Reeves, of Abingdon, who have been married for 70 years.

The couple, both 91, volunteered for the study at Oxford Health NHS Foundation Trust after Mrs Reeves was diagnosed with Alzheimers disease in 2016. Her husband said: Weve become closer as a consequence of her diagnosis because I have become her carer now. The study is not for our benefit particularly, we took part to help others.

In 2018/19, there were 1,930 studies involving 39,129 participants at Oxford University Hospitals NHS Foundation Trust, which manages the John Radcliffe Hospital, Churchill Hospital and Nuffield Orthopaedic Centre in Oxford and Banburys Horton General Hospital.

Professor Keith Channon, director of research and development at the trust, said: Oxford is one of the UKs leading centres for healthcare research, often leading the world in specialties as diverse as neuroscience, cancer, cardiology, diabetes or surgery and delivering improvements in diagnosis and treatment for NHS patients.

ALSO READ: Scientists to share latest dementia research at open day

That research, and the ability to push forward our knowledge of different health conditions, is critically dependent on the participation of many thousands of patients and members of the public from across the region.

We hope that this exhibition, which showcases examples of the ground-breaking research that takes place here, highlights the contributions of patients and members of the public and encourages them to get involved in research studies.

After the Covered Market, the exhibition will travel around the Thames Valley to be displayed at other venues. To find out more visit thebodyunlocked.info.

Read the rest here:
Photo exhibition at Covered Market showcases science research - Oxford Mail

Recommendation and review posted by Bethany Smith

Newark, NJ, Feb. 20, 2020 (GLOBE NEWSWIRE) -- As per the report published by Fior Markets, theglobal veterinary x-ray market is expected to grow from USD 651.07 Million in 2017 to USD 1,167.47 Million by 2025 at a CAGR of 7.81% during the forecast period from 2018-2025.

Radiology systems are the most preferred diagnostic tools a veterinarian uses to diagnose diseases in animals. It contains of diagnostic medical descriptions including ultrasound, magnetic resonance tomography, magnetic resonance imaging and atomic imaging. This is a non-invasive way to diagnose the disease. It is a painless procedure, however, animals are often anesthetized to reduce anxiety and stress during the procedure. The rise in the number of pets and the increase in awareness about the well-being of pets is driving the growth of this sector. According to the American Pet Products Association, in 2016, American families had approximately 35% of cats and 44% of dogs, making them around 85.8 million cats and 78 million dogs owned by the United States

The global market for veterinary X-rays is expected to grow rapidly during the forecast period, due to the increasing incidence of animal bone diseases, the increasing number of pets around the world, and the increase in the number of veterinary practitioners worldwide, as it is the main factor driving the market. The high cost of veterinary X-ray tools and the shortage of skilled veterinary technicians may limit market growth. However, high levels of pet insurance may boost future market opportunities.

DOWNLOAD FREE SAMPLE REPORT AThttps://www.fiormarkets.com/report-detail/376062/request-sample

Key players operating in the global veterinary X-ray market are IDEXX Laboratories, Fujifilm, Onex Corporation, Agfa-Gevaert Group, Sound Technologies, Sedecal, Examion, Canon, DRE Veterinary, Heska Corporation, Fovea, Clearvet, Control-X Medical, Allpro Imaging, Vetel Diagnostics, Pixxgen and Konica Minolta among others. To enhance their market position in the global veterinary X-ray market, the key players are now focusing on adopting the strategies such as recent developments, product innovation, joint venture, mergers & acquisitions, collaborations, and partnership. Major firms are increasingly investing on research and development activities and development of newer products.

Computed radiography systems is dominating the segment and was valued around USD 286.44 Million in 2017

The technology segment is classified into computed radiography systems segment, direct radiography systems and film-based radiography systems. Computed radiography systems is dominating the segment and was valued around USD 286.44 Million in 2017. Increasing demand for affordable digital X-ray equipment and benefits offered by CR systems over other technologies are contributing for the growth of the segment.

The digital X-rays segment held the largest share of around 56.31% in 2017

Type section includes digital X-rays and analog X-rays. The digital X-rays segment held the largest share of around 56.31% in 2017. X-ray systems offer various benefits over analog systems, which include less costly, improved efficiency, and patient-centric imaging are some of the factors driving the growth of the segment.

The Stationary X-Ray Systems segment is dominated and expected to witness the highest market share of 56 % in the forecast period

The segment is classified into stationary x-ray systems and portable x-ray systems. The stationary x-ray systems is dominated and expected to witness the highest market share of 56% in the forecast period. While new technology advancement and rising use of portable x-ray systems are boosting this segment.

The small companion animals segment is dominated and is expected to held largest share of 61.17% in 2017

Animal type segment includes small companion animals and large animals. The small companion animals segment is dominated and is expected to held largest share of 61.17% in 2017. Increased adoption of pets, growing companionship and demand of highly accurate diagnostic solutions are boosting the growth of the segment.

The orthopedic & trauma segment is dominating and was valued around USD 214.83 million in 2017

Application segment is bifurcated into orthopedics & trauma, dental applications, oncology and other applications. Orthopedic & trauma segment is dominating and was valued around USD 214.83 million in 2017 due to increase in injuries among animals and availability of animal care facilities are contributing to the growth of the segment.

The veterinary hospitals & academic institutes segment is anticipated to grow with the highest CAGR of 9.14% in the forecast period

End user section includes veterinary hospitals & academic institutes and veterinary clinics. The veterinary hospitals & academic institutes segment is anticipated to grow with the highest CAGR of 9.14% in the forecast period. The growth can be accredited to developments in technologies for cost-effective, fast and precise diagnostic tools for animal healthcare.

Browse full report with TOC athttps://www.fiormarkets.com/report/global-veterinary-x-ray-market-by-technology-type-direct-376062.html

Regional Segment Analysis of the Veterinary X-ray market

The regions analysed for the market include North America, Europe, South America, Asia Pacific, and Middle East and Africa. North America region captured the largest share of global veterinary X-ray market and was valued in USD 318.99 Million in 2017 whereas Asia pacific is expected to attain the lucrative growth in the forecast period. North America region is expected to dominate the market due to pet adoption coupled with increasing healthcare expenditure and increase in R&D with growing demand for veterinary equipment. Asia pacific is expected to register the highest growth in the forecast period owing to growing demand for veterinary products and availability of low-cost animal health products are anticipated to drive the growth. Figured radiography and film-based radiography are inexpensive in this region as compared to industrialised regions.

About the report:

The global veterinary x-ray market is analysed on the basis of value (USD Million). All the segments have been analyzed on global, regional and country basis. The study includes the analysis of more than 30 countries for each segment. The report offers an in-depth analysis of driving factors, opportunities, restraints, and challenges for gaining the key insight of the market. The study includes porters five forces model, attractiveness analysis, raw material analysis, supply, demand analysis, competitor position grid analysis, distribution and marketing channels analysis.

For Instant Purchase:

Customization of the Report:

The report can be customized as per client requirements. For further queries, you can contact us onsales@fiormarkets.comor +1-201-465-4211. Our executives will be pleased to understand your requirements and offer you the best-suited reports.

About Fior Markets

Fior Markets is a futuristic market intelligence company, helping customers flourish their business strategies and make better decisions using actionable intelligence. With transparent information pool, we meet clients objectives, commitments on high standard and targeting possible prospects for SWOT analysis and market research reports. Fior Markets deploys a wide range of regional and global market intelligence research reports including industries like technology, pharmaceutical, consumer goods, food and beverages, chemicals, media, materials and many others. Our Strategic Intelligence capabilities are purposely planned to boost your business extension and elucidate the vigor of diverse industry. We hold distinguished units of highly expert analysts and consultants according to their respective domains. The global market research reports we provide involve both qualitative and quantitative analysis of current market scenario as per the geographical regions segregated and comprehensive performance in different regions with global approach. In addition, our syndicated research reports offer a packaged guide to keep companies abreast of the upcoming major restyle in their domains. Fior Markets facilitates clients with research analysis that are customized to their exact requirements, specifications and challenges, whether it is comprehensive desk research, survey work, composition of multiple methods, in-detailed interviewing or competitive intelligence. Our research experts are experienced in matching the exact personnel and methodology to your business need.

Contact Us

Avinash DHead of Business DevelopmentPhone:+1-201-465-4211Email:sales@fiormarkets.comWeb:www.fiormarkets.com

To Read Top Industries Reports, Visit our Affiliated Website: https://www.mrinsights.biz/

Related Reports

Global Breast Cancer Liquid Biopsy Market - https://www.fiormarkets.com/report/global-breast-cancer-liquid-biopsy-market-by-circulating-376049.htmlGlobal Cell Therapy Technologies Market - https://www.fiormarkets.com/report/global-cell-therapy-technologies-market-by-product-consumables-376050.htmlGlobal Dental 3D Printing Market - https://www.fiormarkets.com/report/global-dental-3d-printing-market-by-product-and-376051.htmlGlobal Gene Therapy Market - https://www.fiormarkets.com/report/global-gene-therapy-market-by-type-germline-gene-376052.html

See the original post here:
Global Veterinary X-ray Market is Expected to Reach USD 1,167.47 Million by 2025 : Fior Markets - GlobeNewswire

Recommendation and review posted by Bethany Smith

Global CNS Gene Therapy Market From PMRs Viewpoint

Decorated with a team of 300+ analysts, PMR Insights serves each and every requirement of the clients while preparing market reports. With digital intelligence solutions, we offer actionable insights to our customers that help them in overcoming market challenges. Our dedicated team of professionals perform an extensive survey for gathering accurate information associated with the market.

PMR, in its latest business report elaborates the current situation of the global CNS Gene Therapy market in terms of volume (x units), value (Mn/Bn USD), production, and consumption. The report scrutinizes the market into various segments, end uses, regions and players on the basis of demand pattern, and future prospect.

In this CNS Gene Therapy market study, the following years are considered to project the market footprint:

Request Sample Report @ https://www.persistencemarketresearch.co/samples/27514

On the basis of product type, the global CNS Gene Therapy market report covers the key segments,

key players and product offerings

Request Report Methodology @ https://www.persistencemarketresearch.co/methodology/27514

The CNS Gene Therapy market research addresses the following queries:

After reading the CNS Gene Therapy market report, readers can

CNS Gene Therapy market players Player 1, Player 2, Player 3, and Player 4, among others represent the global CNS Gene Therapy market. The market study depicts an extensive analysis of all the players running in the CNS Gene Therapy market report based on distribution channels, local network, innovative launches, industrial penetration, production methods, and revenue generation. Further, the market strategies, and mergers & acquisitions associated with the players are enclosed in the CNS Gene Therapy market report.

For any queries get in touch with Industry Expert @ https://www.persistencemarketresearch.co/ask-an-expert/27514

About us:

PMR is a third-platform research firm. Our research model is a unique collaboration of data analytics and market research methodology to help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Contact us:

305 Broadway, 7th Floor

New York City, NY 10007

United States

Ph.no. +1-646-568-7751

Originally posted here:
CNS Gene Therapy Market Growth Factors, Applications, Regional Analysis, Key Players and Forecasts by 2026 - Jewish Life News

Recommendation and review posted by Bethany Smith

GlobalSandhoff disease treatment marketis growing at a steady CAGR in the forecast period of 2019-2026. The report contains data of the base year 2018 and historic year 2017. This rise in market value can be attributed to the orphan drug designation to novel drugs, along with the increasing investment of biotechnology and pharmaceutical industries in R&D.

The key market players in the Sandhoff disease treatment market areIntrabio, Axovant Gene Therapies Ltd among others

Get Exclusive Sample Report Herehttps://www.databridgemarketresearch.com/request-a-sample?dbmr=global-sandhoff-disease-treatment-market&raksh

With the market info provided in the Sandhoff Disease Treatment Market report, it has become easy to gain global perspective for the international business. Focus groups and in-depth interviews are included for qualitative analysis whereas customer survey and analysis of secondary data has been carried out under quantitative analysis. This market analysis report acts as a very significant constituent of business strategy. It is a definite study of the Healthcare industry which explains what the market definition, classifications, applications, engagements, and global industry trends are. Sandhoff Disease Treatment Market business document proves to be a sure aspect to help grow the business.

Market Definition: Global Sandhoff Disease Treatment Market

Sandhoff diseaseis also known as Beta-hexosaminidase-beta-subunit deficiency is a fatal pediatric lysosomal storage genetic disorder characterized by progressively destruction of neuron in the brain and spinal cord. It is caused by defects in HEXB gene which is responsible for regulation of vital enzyme called beta-hexosaminidase, as a result of accumulation of lipid called G2 gangliosides. This ongoing accumulation of lipid affects the function of the nerve cells and causes other neurological problem.

Segmentation:Global Sandhoff Disease Treatment Market

Sandhoff Disease Treatment Market : By Types

Sandhoff Disease Treatment Market : ByTherapy

Sandhoff Disease Treatment Market : By Treatment

Sandhoff Disease Treatment Market : By Drugs

Sandhoff Disease Treatment Market : ByRoute of Administration

Sandhoff Disease Treatment Market : By Distribution Channel

Sandhoff Disease Treatment Market : By End-Users

Sandhoff Disease Treatment Market : By Geography

Table of Contents is Available[emailprotected]https://www.databridgemarketresearch.com/toc?dbmr=global-sandhoff-disease-treatment-market&raksh

Key Developments in the Sandhoff Disease Treatment Market

Sandhoff Disease Treatment Market Drivers

Sandhoff Disease Treatment Market Restraints

Sandhoff Disease Treatment Market : Competitive Analysis

Global Sandhoff disease treatment market is highly fragmented and the major players have used various strategies such as new product launches, expansions, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of Sandhoff disease treatment for Global, Europe, North America, Asia-Pacific, South America and Middle East & Africa.

Opportunities in the Sandhoff Disease Treatment Market :-

Want Full Report? Enquire Here @https://www.databridgemarketresearch.com/inquire-before-buying?dbmr=global-sandhoff-disease-treatment-market&raksh

About Data Bridge Market Research:

Data Bridge Market Researchis a versatile market research and consulting firm with over 500 analysts working in different industries. We have catered more than 40% of the fortune 500 companies globally and have a network of more than 5000+ clientele around the globe. Our coverage of industries include Medical Devices, Pharmaceuticals, Biotechnology, Semiconductors, Machinery, Information and Communication Technology, Automobiles and Automotive, Chemical and Material, Packaging, Food and Beverages, Cosmetics, Specialty Chemicals, Fast Moving Consumer Goods, Robotics, among many others.

Data Bridge adepts in creating satisfied clients who reckon upon our services and rely on our hard work with certitude.We are content with our glorious 99.9 % client satisfying rate.

Contact Us

Data Bridge Market Research

US: +1 888 387 2818

UK: +44 208 089 1725

Hong Kong: +852 8192 7475Mail:[emailprotected]

Visit link:
Sandhoff Disease Treatment Market 2020-2026 Boosting the Growth Worldwide || Leading Players Intrabio, Axovant Gene Therapies Ltd - News Times

Recommendation and review posted by Bethany Smith