Italian neurosurgeon Sergio Canavero will undertake the first human head transplant later this year in China, the doctor told German magazineOoomin an article published Thursday. And, following that effort, he will revive a cryogenically frozen brain and transplant it into a donor body within the next three years.

The plans, completely disconnected from reality and the state of modern medicine, are at least in line with his previous outlandish goals and dubious animal research.

Canavero made headlines in the past few years by claiming that transplanting the whole head of a human onto a donor body is currently possible. A Russian man, suffering from a spinal muscular atrophy malady called Werdnig-Hoffmann Disease, even publicly volunteered for the procedure.

As proof that the transplant could work, Canavero published gruesome experiments in 2016, said to have repaired the severely injured spinal cords of mice, rats, and a dog. The experiments came complete with cringe-worthy video of recovering animals struggling to drag their limp bodies around. Yet, the study lacked controls, detailed methods, and data on the injuries and recoveries. Canavero claimed to perform a head transplant on a monkey but did not publish the experiment.

Mouse limping after experimental spinal cord repair.

Sergio Canavero giving a TEDX talk.

Sergio Canavero with his Chinese partner, Dr. Xiaoping Ren, who will lead the operation team onsite during an attempted head transplant procedure.

Experts decidedly consider his research on spinal cord repair, let alone whole head transplants, unconvincing. A medical ethicist dubbed Canavero out of his mind for sweeping past the currently insurmountable challenges of such feats. These include intricately repairing and reattaching thousands of delicate nerves and restoring function. Right now, doctors cant even convince the immune system to accept far simpler transplants consistently. Theres also the completely unknown effects of such a transplant on the powerful human psyche.

Canavero is carrying on, undeterred it seems. In his Ooom interview, he not only glided through the idea of successfully transplanting a head, he made an even more absurd claim: that he would revive a cryogenically frozen brain and transplant it into a donor body. Canavero said he would obtain a preserved brain from Alcor Life Extension Foundation, a cryonics company located in Scottsdale, Arizona, according to Gizmodo.

There is currently no way to revive and molecularly repair a frozen human brain. And such transplants havent even been attempted in animals. Thus, the surgical procedure is decades if not centuries away.

As Gizmodo also reports, Alcor said that Canavera hadnt even contacted the company. It distanced itself from the doctor, as did other cryonics leaders, and noted that his efforts are not realistic or even a shared goal.

In a statement, the company said:

The Alcor Life Extension has had no contact with Dr. Canavero. It is not yet possible to revive human brains cryopreserved with present methods. Revival of todays cryonics patients will require future repair by highly advanced future technology, such as molecular nanotechnology. Technology that is advanced enough to repair a cryopreserved brain would by its nature also be able to regrow new tissues, organs, and a healthy body for the revived person. Therefore Alcor does not expect body donations or transplants to ever be necessary for revival of cryonics patients. Until advanced tissue regeneration technology is developed, we wish Dr. Canavero well in his development of body transplant surgery for living patients today who might benefit.

The rest is here:
Out of his mind surgeon plans human head transplant, revival of frozen brain - Ars Technica

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Regenxbio Inc (RGNX) Stock Rating Upgraded by Zacks Investment Research The Cerbat Gem The Company focuses on the development, commercialization and licensing of recombinant adeno-associated virus gene therapy. Its products candidates include RGX-501, for the treatment of homozygous familial hypercholesterolemia which uses the AAV8 ... Vittal Vasista Sells 3100 Shares of Regenxbio Inc (RGNX) StockTranscript Daily all 14 news articles »

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Regenxbio Inc (RGNX) Stock Rating Upgraded by Zacks Investment Research - The Cerbat Gem

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Brigham and Women's Hospital in Boston.

BRIAN SNYDER/REUTERS/Newscom

By Kelly ServickApr. 27, 2017 , 5:00 PM

A research misconduct investigation of a prominent stem cell lab by the Harvard Universityaffiliated Brigham and Womens Hospital (BWH) in Boston has led to a massive settlement with the U.S. government over allegations of fraudulently obtained federal grants. As Retraction Watch reports, BWH and its parent health care system have agreed to pay $10 million to resolve allegations that former BWH cardiac stem cell scientist Piero Anversa and former lab members Annarosa Leri and Jan Kajstura relied on manipulated and fabricated data in grant applications submitted to the U.S. National Institutes of Health (NIH).

A statement from the U.S. Attorneys Office for the District of Massachusetts released today notes that it was BWH itself that shared the allegations against Anversas lab with the government. The hospital had been conducting its own probe into the Anversa lab since at least 2014, when a retraction published in the journal Circulation revealed the ongoing investigation. The hospital has not yet released any findings.

In 2014, Anversa and Leri sued Harvard and BWHalong with BWH President Elizabeth Nabel and Gretchen Brodnicki, Harvards dean for faculty and research integrityfor launching and publicizing the investigation that they claimed wrongfully damaged their careers. In their complaint, they acknowledged fabricated data in the Circulation paper and altered figures in a 2011 paper for whichThe Lancethas published an expression of concern. But they claimed that Kajstura had altered data without their knowledge. (Anversa and Leris recent papers list their institution as Swiss Institute for Regenerative Medicine, Retraction Watch notes.)

In July 2015, a federal district court judge dismissed the lawsuit, ruling that the plaintiffs had to first air their grievances with the federal Office of Research Integrity, which handles misconduct investigations at NIH-funded labs.

Grant fraud cases against universities rarely involve research misconduct, and most are brought by whistleblowers who stand to claim a share of any returned funds. Despite the high penalty, BWH gets praise from the Department of Justice in todays announcement for self-disclosing the allegations and for taking steps to prevent future recurrences of such conduct.

But the result is confusing and potentially discouraging, says Ferric Fang, a microbiologist at the University of Washington in Seattle, who has published several analyses of retractions, misconduct, and the scientific enterprise. It sounds as if the researchers themselves were found to have engaged in improper practices, but the institution is on the hook for the settlement. The decision deserves greater clarification, he says, or it could discourage other institutions from being as forthcoming in the future.

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$10 million settlement over alleged misconduct in Boston heart stem cell lab - Science Magazine

Recommendation and review posted by Bethany Smith

The patches may be effective at helping to restore the heart following a myocardial infarction, as the heart isnt able to restore lost cells on its own. The patches may be effective at helping to restore the heart following a myocardial infarction, as the heart isnt able to restore lost cells on its own.

A team of researchers from University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham have developed a technique for 3D printing cardiac patches seeded with living cells. The patches may be effective at helping to restore the heart following a myocardial infarction, as the heart isnt able to restore lost cells on its own.

The technology has already been tested on a mouse model following an induced heart attack in which cardiac function wa significantly improved in four weeks following the application of the patch.

The patch is structurally based on how proteins naturally assemble within cardiac tissue. A highly detailed technique called multiphoton-excited 3D printing was used to create an extracellular matrix that was then seeded with about 50,000 cardiomyocytes, smooth muscle cells, and endothelial cells obtained from human-induced pluripotent stem cells.

The patch began beating on its own only a day after placing the cells and calcium transients, which are intercellular signaling mechanisms, were detected and increased over the following week.

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3D Printed Patches seeded with cells to repair cardiac tissue after heart attacks - BSA bureau (press release)

Recommendation and review posted by Bethany Smith

SOUTH SAN FRANCISCO, CA--(Marketwired - April 27, 2017) - VistaGen Therapeutics Inc. (VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, announced today the peer-reviewed publication of nonclinical studies of the effects of AV-101 (4-Cl-KYN), its CNS prodrug candidate, in four well-established nonclinical models of pain.

The publication, titled: "Characterization of the effects of L-4-chlorokynurenine on nociception in rodents," by lead author, Tony L. Yaksh, Ph.D., and co-authors, Robert Schwarcz, Ph.D. and H. Ralph Snodgrass, Ph.D., was recently published in The Journal of Pain (DOI: 10.1016/j.jpain.2017.03.014) and is available online at http://www.jpain.org/article/S1526-5900(17)30552-7/abstract.

"In these studies, AV-101 was found to have robust anti-nociceptive effects, similar to gabapentin, but with a better side effect profile in several pre-clinical models of hyperalgesia and allodynia, results suggest AV-101's potential for treating multiple hyperpathic pain states," reported Tony L. Yaksh, Ph.D., Professor in Anesthesiology at the University of California, San Diego (UCSD).

"In comparison to gabapentin and other agents commonly used by millions of patients battling chronic neuropathic pain, we believe AV-101 has the potential to reduce debilitating pain effectively without causing burdensome side effects. Many neuropathic pain treatments on the market today have side effects, including anxiety, depression, mild cognitive impairment and sedation. The positive results published in these studies fall in line with our goal of advancing Phase 2 clinical development of AV-101 across a broad range of CNS indications, including major depressive disorder, neuropathic pain and L-DOPA-induced dyskinesia associated with Parkinson's disease. We are optimistic that we will be able to bring to market a new generation CNS medication that would help millions of patients currently treated with therapies with inadequate efficacy and significant side effects and safety concerns," stated H. Ralph Snodgrass, Ph.D., VistaGen's President and Chief Scientific Officer.

Study Summary and Key Findings:

About AV-101

AV-101 (4-CI-KYN) is an oral CNS prodrug candidate in Phase 2 development in the U.S. as a new generation treatment for major depressive disorder (MDD). AV-101 also has broad potential utility in several other CNS disorders, including chronic neuropathic pain and epilepsy, as well as addressing symptoms associated with neurodegenerative diseases, such as Parkinson's disease and Huntington's disease.

AV-101 is currently being evaluated in a Phase 2 monotherapy study in MDD, a study being fully funded by the U.S. National Institute of Mental Health (NIMH) and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH, as Principal Investigator.

VistaGen is preparing to advance AV-101 into a 180-patient, U.S. multi-center, Phase 2 adjunctive treatment study in MDD patients with an inadequate response to standard FDA-approved antidepressants, with Dr. Maurizio Fava of Harvard University as Principal Investigator.

About VistaGen

VistaGen Therapeutics, Inc. (VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. VistaGen's lead CNS product candidate, AV-101, is in Phase 2 development as a new generation oral antidepressant drug candidate for major depressive disorder (MDD). AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2 monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 180-patient Phase 2 study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressants. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Company's Phase 2 adjunctive treatment study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, and symptoms of Parkinson's disease and Huntington's disease, where modulation of the NMDAR, AMPA pathway and/or key active metabolites of AV-101 may achieve therapeutic benefit.

Read More

VistaStem Therapeutics is VistaGen's wholly owned subsidiary focused on applying human pluripotent stem cell technology, internally and with collaborators, to discover, rescue, develop and commercialize proprietary new chemical entities (NCEs), including small molecule NCEs with regenerative potential, for CNS and other diseases, and cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. In December 2016, VistaGen exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease.

For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking Statements

The statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2 (monotherapy) and/or the Company's planned Phase 2 (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, including neuropathic pain and L-DOPA-induced dyskinesia associated with Parkinson's disease, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the Phase 2 clinical development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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VistaGen Therapeutics Announces Peer-Reviewed Publication in ... - Yahoo Finance

Recommendation and review posted by simmons

Ten years ago, the bones currently in your body did not actually exist. Like skin, bone is constantly renewing itself, shedding old tissue and growing it anew from stem cells in the bone marrow. Now, a new technique developed at Caltech can render intact bones transparent, allowing researchers to observe these stem cells within their environment. The method is a breakthrough for testing new drugs to combat diseases like osteoporosis.

The research was done in the laboratory of Viviana Gradinaru (BS '05), assistant professor of biology and biological engineering and a Heritage Medical Research Institute Investigator. It appears in a paper in the April 26 issue of Science Translational Medicine.

In healthy bone, a delicate balance exists between the cells that build bone mass and the cells that break down old bone in a continual remodeling cycle. This process is partially controlled by stem cells in bone marrow, called osteoprogenitors, that develop into osteoblasts or osteocytes, which regulate and maintain the skeleton. To better understand diseases like osteoporosis, which occurs when loss of bone mass leads to a high risk of fractures, it is crucial to study the behavior of stem cells in bone marrow. However, this population is rare and not distributed uniformly throughout the bone.

"Because of the sparsity of the stem cell population in the bone, it is challenging to extrapolate their numbers and positions from just a few slices of bone," says Alon Greenbaum, postdoctoral scholar in biology and biological engineering and co-first author on the paper. "Additionally, slicing into bone causes deterioration and loses the complex and three-dimensional environment of the stem cell inside the bone. So there is a need to see inside intact tissue."

To do this, the team built upon a technique called CLARITY, originally developed for clearing brain tissue during Gradinaru's postgraduate work at Stanford University. CLARITY renders soft tissues, such as brain, transparent by removing opaque molecules called lipids from cells while also providing structural support by an infusion of a clear hydrogel mesh. Gradinaru's group at Caltech later expanded the method to make all of the soft tissue in a mouse's body transparent. The team next set out to develop a way to clear hard tissues, like the bone that makes up our skeleton.

In the work described in the new paper, the team began with bones taken from postmortem transgenic mice. These mice were genetically engineered to have their stem cells fluoresce red so that they could be easily imaged. The team examined the femur and tibia, as well as the bones of the vertebral column; each of the samples was about a few centimeters long. First, the researchers removed calcium from the bones: calcium contributes to opacity, and bone tissue has a much higher amount of calcium than soft tissues. Next, because lipids also provide tissues with structure, the team infused the bone with a hydrogel that locked cellular components like proteins and nucleic acids into place and preserved the architecture of the samples. Finally, a gentle detergent was flowed throughout the bone to wash away the lipids, leaving the bone transparent to the eye. For imaging the cleared bones, the team built a custom light- sheet microscope for fast and high-resolution visualization that would not damage the fluorescent signal. The cleared bones revealed a constellation of red fluorescing stem cells inside.

The group collaborated with researchers at the biotechnology company Amgen to use the method, named Bone CLARITY, to test a new drug developed for treating osteoporosis, which affects millions of Americans per year.

"Our collaborators at Amgen sent us a new therapeutic that increases bone mass," says Ken Chan, graduate student and co-first author of the paper. "However, the effect of these therapeutics on the stem cell population was unclear. We reasoned that they might be increasing the proliferation of stem cells." To test this, the researchers gave one group of mice the treatment and, using Bone CLARITY, compared their vertebral columns with bones from a control group of animals that did not get the drug. "We saw that indeed there was an increase in stem cells with this drug," he says. "Monitoring stem cell responses to these kinds of drugs is crucial because early increases in proliferation are expected while new bone is being built, but long-term proliferation can lead to cancer."

The technique has promising applications for understanding how bones interact with the rest of the body.

"Biologists are beginning to discover that bones are not just structural supports," says Gradinaru, who also serves as the director of the Center for Molecular and Cellular Neuroscience at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. "For example, hormones from bone send the brain signals to regulate appetite, and studying the interface between the skull and the brain is a vital part of neuroscience. It is our hope that Bone CLARITY will help break new ground in understanding the inner workings of these important organs."

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Transparent Bones Enable Researchers to Observe Stem Cells Inside - Laboratory Equipment

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A local stem cell study is changing the future of orthopedics.

A new study taking place at the Andrews Institute in Northwest Florida could shape the future of orthopedic surgery.

The goal of the study, spearheaded by Dr. Adam Anz and already eight years in the making, is to use stem cells to regrow cartilage.

If approved, it will be the first orthopedics study of its kind done in the United States and only the second in the entire world.

Stem cells are currently utilized most in cancer research and treatments, but Dr. Anz of the Andrews Institute wants to change that by putting regenerative medicine to the test, using stem cells to regrow knee cartilage.

The Andrews Institute already uses stem cells in certain therapies, but this new method could be a game changer.

"The bone marrow aspirate, which we're studying for knee arthritis and we can offer to patients, is the 1990's technology of stem cells," Dr. Anz said. "What we're studying is the modern way to harvest many more stem cells. That's the reason the FDA has said you need to bring this through our process before you just offer it to people."

Through a process called apheresis, stem cells are harvested from the patient with help from a synthetic hormone that promotes the body to generate more stem cells.

"Through this process we can collect millions of cells," Dr. Anz said. "Just 140 milliliters -- about a half of a coke can -- will have 140 million stem cells."

The stem cells will then be sorted, divided and injected into the patient's knee. Excess cells are stored in a nitrogen freezer at negative 181 degrees Celsius until the next round of injections, a process to be repeated over the next two years.

"If this study is successful, this will be the first approved in orthopedics in the United States," said Dr. Anz.

The study begins in May. Dr. Anz believes it will take about another five to seven years before the FDA can approve it for use in patients.

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Groundbreaking stem cell study kicks off in Northwest Florida - WEAR

Recommendation and review posted by simmons

N

ow you see it, now you dont: Scientists have used a chemical technique to make mouse bones turn transparent. The technique has been used in the past to make brains and kidneyssee-through, but this marks the first time its been used in hard tissues.

The ability to see within a bone couldhave implications for research into bone diseases, by letting researchers get a more accurate picture of bones internal structure.

The technique is called CLARITY, and since 2013, when it was first described, it has been deployed on a wide variety of mammalian tissues and inplants. Caltech neuroscientistViviana Gradinaru, an original developer of the technique, even cleared an entire mouses body in 2014 (except for its bones, which were unaffected, she said).

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The approach works by chemically locking proteins and DNA in place with a hydrogel, after which researchers wash away fats within the tissue. Lipids refract light, so this washing step makes CLARITY-treated tissues transparent.

Flexible 3-D printed scaffolds could mend broken bones

In this case, Gradinaruwanted to look at bone marrow and count the number of stem cells that could ultimately produce new bone cells.

Bone is not a static organ. It iscontinuously changed. The bones we have in our body, we didnt have them 10 years ago, she explained. Acontinuous process of bone cell death and bone cell growth ishappening, spurred by progenitor cells in a bones soft, spongy marrow.

But looking for these cells can bechallenging. There arent that many progenitor cells, soextrapolating the number and distribution based ona small sample isnt ideal. Researchers can slice the bone, but cuttingcan damage the edges. Putting images of the sliced bones back together into a coherent, 3-D picture is very difficult, too.A clear bone avoidsslicing altogether.

Doug Richardson, director of imaging at the Harvard Center for Biological Imaging, said the paper represented a step forward in bone clearing. (Richardson was not involved in this research.)

This technique has the potential to monitor bone health or disease progression over larger volumes with greater accuracy, he said.

Gradinarus team has already demonstrated one possible application. They found that a drug for osteoporosis, currently being developed by Amgen, triggered an increase in the number of stem cells in CLARITY-treated bone.Some Amgen scientists were coauthors of the paper.

Using CLARITY let the team more effectively measure the rate of this increase.This is very important, because you want a controlled increase too much of an increase can lead to tumors, Gradinarusaid.

Other uses could be on the horizon. Being able to make a mouse or rat skull see-through could be useful for Gradinarus fellow neuroscientists who use implants in their research and want to establish the exact position of the impact after experiments are done.

Theres still more work to be done. For instance, finding a way to tagthe samples with antibodies without having to cut a bone in half, as researchers did in this paper would be ideal.Gradinaru also wouldnt mind some speed improvements:In this case, the CLARITY process took nearly a month.

Its not a fast method, by any means, Gradinaru said. However, the result theres no substitute for getting 3-D access to the intact bone marrow.

Kate Sheridan can be reached at kate.sheridan@statnews.com Follow Kate on Twitter @sheridan_kate

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Caroline, 11, Elizabeth, 3, Jon Thomas, 13 and James Christopher Allums, 20, do everything as a family. James Christopher and Elizabeth both have a rare medical condition. Their mother, Ellen Allums, said they all go through the process together and support each other with faith and love.(Photo: Courtesy)

Learning that your child has a rare, life-threatening illness is difficult for any family. Everything changes. One family learned that two of their children share the same rare blood disorder.

"That news that we heard was the worst news that we could hear, but it was the best thing that's ever happened to us. It really changed our perspective. It changed our priorities," Chris Allums said.

"We're no longer the same people we were," Ellen Allums said.

Ellen and Chrishave four childrenJames Christopher, 20,Jon Thomas, 13,Caroline,11, andElizabeth, 3.

James Christopher and Elizabeth have Fanconi anemia, a disease that affects the bone marrow's ability to produce blood. Bone marrow or blood stem cell transplants are considered the best treatments, andthey have not yet found a match for either child.

James Christopher was diagnosed 12 years ago and told he had about 18 monthsto live. The family was told he must received a bone marrow transplant.

"We immediately decided that, first of all, we're going to pray and expect a miracle and grow our faith, and next, we're going to try and see if we can find him a bone marrow match and help others along the way, see how many lives that we can affect, that we can save both spiritually and physically," Ellen said.

More than 16,000 people have been added to the worldwide bone marrow registry as a result of drives held on behalf of the Allums. Ellen said they know of at least 41 lives that have been saved because of those efforts, and they're asking more people to commit to donate.

'Looking for a double miracle'

Ellen said a doctor said someone with FA can be like a duck gliding on the water the surface appearance is calm, but people can't see all the effort that goes into staying in motion.

It has a variety of symptoms such as fatigueand can lead to bone marrow or organ failure. Ellen and Chris said FA patients are 500 times more likely to develop some cancers, such as leukemia. James Christopher is subject to constant screenings.

The disease is genetic. According to the National Organization for Rare Disorders, the incidence rate is 1 in 136,000 births. Ellen said her children are two ofsix in Louisiana affected by FA.

Elizabeth's blood counts have been OK, but doctors have said James Christopher has an immediate need for a transplant. DNA needs to be close to an exact match, and many families find a relative who can donate.Elizabeth is a 100 percent match, but she's ineligible because of her FA.

One donor, once found, could help both.A bone marrow transplant won't cure someone with FA, but it can help prolong life.

"Just because you're having to wait doesn't mean the miracle's not going to come. We've been waiting 12 years, but we still have faith that that miracle's coming. Just because it hasn't happened doesn't mean it's not going to. The timing needs to be right," Ellen said. "In our lives, we're looking for an even greater miracle because we're looking for a double miracle, with two children."

FA patients can require blood and platelet transfusions, after which they may become dependent and need additional rounds, which would require a bone marrow transplant quickly.

James Christopher received his first blood transfusion three weeks ago.

"Chris gave. His daddy gave blood to him, and we felt like it was his heavenly father and his earthly father that gave him that blood, and now we're praying and believing that he never has to receive it again," Ellen said.

She said they've dealt with some scary bleeding issues "like Niagara Falls," and James Christopher has almost lost his life a few times. His parents call him a survivor, a warrior. He gets up and stays active daily, even with low blood counts that doctors thinkwould cause fatigue.

"I love to prove doctors wrong. If they give me a boundary, I want to cross it, definitely, when it comes to that," he said. He likes to tell people "keep calm and carry on," like the World War II posters.

Every bump, scratch, scrape and bruise for the siblings is noteworthy, and the whole family works to avoid germs. A simple cough or cold could be devastating, so they're all in tune to notice illness.They're very aware of the importance of handwashing and staying home if ill. Chris said during cold and flu season, they often come in, shower and change clothes before interacting with the others.

Ellen said they respect people who choose not to vaccinate, but all of her children have been vaccinated because measles or chicken pox can kill someone with FA.

All the children home school to help prevent illness. When James Christopher was diagnosed, doctors said it could help him live longer. Chris said all four have excelled fromthe one-on-one time, and they've enjoyed getting to know other families inthe Christian Homeschool Association.

The Allums know their lives are different than those of many other families, but they are running their own race.

"I have to tell you that we have a wonderful life. Sure it's full of hard work, but it's wonderful because of what the Lord has done with it," Chris said.

Read more:Mom says prayer pulled her through transplant|Facing the storm: Mother shares unbelievable story|Big brother to the rescue: Man gives sister half of liver|Man saves 10 in life, death

Joy in the journey

The couple did their homework on hospitals that specialize in the disease and settled on Memorial Sloan Kettering Hospital's cancer center in New York. It had the best survival rates, and they've been going for 12 years.

James Christopher's and Elizabeth's immunity is low, the family cannot travel with the general public. They either have to make the almost 20-hour drive or arrange for a private plane. Ellen said they've had to go there, at times, every three to six months.

The whole family travels to medical appointments.

"Although they don't have the disease, they go through it with them," Ellen said of Jon Thomas and Caroline. She said all of her children have gone to hospitals and played with and prayed for children were facing terminal diagnoses. It's been a blessing to them and a ministry to others.

James Christopher said they try to find fun in the journey. Ellen said they do something fun every time they go to the hospital and embrace John 10:10Jesus came that we might have life and have it abundantly.

James Christopher Allums, 20, holds his sister Elizabeth Allums, 3. The siblings both have a rare medical condition called Fanconi anemia.(Photo: Courtesy)

What happens if there's a match?

"We would be moving to New York for six to eight months for the bone marrow transplant," Ellen said.

Ellen said the a bone marrow recipient with FA will have to go through chemotheraphy for two weeks to kill off the patient's natural bone marrow.

"When the cells are dead, then they receive someone else's bone marrow. It's a liquid, it looks just like an IV, and they lie there and you just pray to God that it's going to take," she said.

After the transplant, the patient is in isolation for 30-40 days. They stay at the transplant hospital for six to eight months and keep a medical mask on for one year. Chris said you hope graph vs. host disease isn't an issue.

Saving lives

She said she used to look at missions that dig wells in other countries and wish they could go save lives, but, after prayer, she realized they are saving people. With the help of family and friends, efforts to add bone marrow donors have helped dozens of people.

"I like to tell people 'You could be the reason someone lives.' ... And I think those words are pretty powerful" Ellen said.

She said the process to donate blood stem cells, which is the most common donation method, involves a needle in each arm for four to six hours.

"It's not even a surgery. It's not like giving a kidney or a lung or a heart, even, but the benefits are that strong. It can truly save a life, but yet all you have to do is like giving blood," Ellen said.

To test for a match, she said, it's even less of a commitment. It takes about five minutes to fill out paperwork and provide a swap from inside the cheek. Anyone 18-55 in good health can register.

The community has come together to help organize a drive for May 1, National Fanconi Anemia Day. A massive drive will take place at more than a dozen locations across northeastern Louisiana, and CenturyLink will be registering employees on-site.Anyone anywhere can order testing kitsonline atdkms.orgorbethematch.org.

A month after testing, people will get a phone call to confirm their position on the registry. Ellen said they pray people will make the commitment.Previous drives for the Allumshave set national records for most registered in one day. Over three days, they tested 5,000 people.

"When people come, we want to educate them on the processin hopes thatwhetherthey are a match in a month or a match in 20 yearsthat they will be committed to beingon that registry to help somebody," Chris said.

They heard of a woman who registered with her family at a previous event andlater developed leukemia. Her sister was found as an instant bone marrow match because theyalreadyhad been tested.

Ellen and Chris said knowing that 41 lives were saved as a result of their family'sefforts makes it all worth it, even though it hasn't been easy.

"But we believe that God is going to heal them both because He told us He would, and we believe that. We hold on to those promises of God. ... and we focus on that. That gives us strength," Ellen said.

Follow Bonnie Bolden on Twitter@Bonnie_Bolden_and on Facebook athttp://on.fb.me/1RtsEEP.

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May 1 is National Fanconi Anemia Day, and a more than a dozen locations across northeastern Louisiana will be part of a single registration drive. Times vary and new locations may be added. Check The Friends of James Christopher and Elizabeth Allumson Facebook or visitcaringbridge.organd searchJames Christopher Allums.

Or order a testing kit online at dkms.org or bethematch.org.

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Family seeks 'miracle' for siblings, saves lives in the process - Monroe News Star

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Ten years ago, the topic of stem cells was shrouded in mystery, but now they're at the forefront of some of the latest innovations in biologyand medicine. Stem cellshave yet to change into a specific type of cell, such as a brain or skin cell. As a result, doctors can manipulate them into, well, any type of cellthey want. However, the way that stem cells are being manipulated is anything but simple. Here is a run-downof fiveof the most fascinating stem cell innovations fromthe past year.

Teeth are necessary for helping uschew our food, but once they fall out. they're useless; or not? The practice of tooth saving, or cryopreserving, has gained popularity, and forgood reason. New research suggests the stem cells found in the pulp of teeth could be used to help people regrow their adult teeth (rather than needing a crown or dentures), and may even have other potentially life-saving regenerative medical benefits, CNN reported.

While still in its early stages, the idea behind tooth preservation is that no other stem cells work better than your own. By saving your baby teeth, oradult teeth that need to be removed through surgery, you may later harvest stem cells that may be used to fight certain cancers or even astherapy for brain injuries.

Read: Stem Cell Research: What Are Stem Cells And Why Is There So Much Controversy

Leukemia is a type of cancer of the blood, and it starts in the bone marrow, which is where our stem cells originate. Traditional leukemia treatment involves a combination of chemotherapy and radiotherapy, but earlier this year doctors at Londons Great Ormond Street hospital believe theycured two babies of leukemia using a new stem cell treatment, Technology Review reported.

The treatment involves taking stem cells from a donor and genetically altering them before injecting them into a patient. These cells are altered so that they are able toattack cancer.

Stem cells are at the forefront of many medical innovations. Photo Courtesy of Pixabay

According to Euro Stem Cell, in traditional stem cell treatments for leukemia patients, cells are taken from donors and then transformed into special cancer-fighting cells; however,this process takes time something many seriously illcancer patients do not have. The Great Ormond Street team hopes that taking stem cells from donors and genetically altering them into hundreds of doses of cancer-fighting cells will create a reserve oftreatments available toanyone who needs them.

According to a study released last year, researchers at Washington University School of Medicine in St. Louis and Harvard University were able to change stem cells derived from the skin of diabetes patients into insulin-secreting cells.

Type 1 diabeticscannot create insulin, which is why patients must inject themselves with this hormone throughout the day. Although this new treatment is still being researched, injecting these stem-cell derived insulin-secreting cells into diabetes patients could control blood sugar without the need formedication.

Stem cellstheoretically can be turned into any type of cell, and as suggested by a 2016 project, this includes brain cells. The project, headed by a team at Bioquark Inc and Revita Life Science India,intendsto regenerate the brain cells of 20 patients that have been declared brain dead from a traumatic brain injury to see whether or not their central nervous systems can be restored, The Telegraph reported.

The team hope the stem cells will grow into new brain cells to replace thedead cells in the brain. While the treatment wouldn't restore these brain-dead patients back to life, the research may lead the way tonew therapies for patients in vegetative states or with certain degenerative conditions.

Brain balls are basically what they sound like;tiny little brains in the shape of balls. According to Wired, they are one of the newest innovations in stem cell research and could hold the answer to treating a variety of medical conditions.

These brain balls are created by coaxing a bunch of stem cells into becoming brain cells, and then using these mini brains to better understand how different diseases affect the brain. For example, according to Wired, these brain balls are ideal for studying conditions such as the Zika virus as scientists can see what's actually happening in an infected brain, but on a much smaller scale.

See Also:

Stem Cells Of Type 1 Diabetes Patients Transformed Into Insulin-Secreting Beta Cells; Research May Lead To New Therapy

Scientists Discover Method To 'Expand' Stem Cells In The Laboratory That Could Lead To New Cancer Treatments

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5 Stem Cell Innovations From The Past Year, From Cancer Treatment To Diabetes Therapy - Medical Daily

Recommendation and review posted by sam

NEW YORK & PITTSBURGH--(BUSINESS WIRE)--RenovaCare, Inc., (OTCQB: RCAR), highlighted an analysis of treatment results on a variety of wide-area and severe burn injuries published in Burns, the peer-reviewed Journal of the International Society for Burn Injuries. The treatment method, which involved isolating and spraying the patients own skin stem cells on the burn wounds, is the technology underlying RenovaCares patented CellMist and SkinGun*.

The early cell spray technology which was used to successfully treat a wide spectrum of burn injuries to some of the largest body areas ever treated with stem cell transplantation, has been engineered into todays RenovaCare SkinGun device, explained Mr. Thomas Bold, President and CEO of RenovaCare, Inc.

The results, published in August 2016, report the retrospective analysis of outcomes in 45 severe second-degree burn patients who received skin stem cell spray grafting treatment under an innovative practice approach.

The patients suffered burn wounds such as gas and chemical explosions, as well as electrical, gasoline, hot water and tar scalding burns. Click here to see before-after photos

In the case of one patient with severe electrical burns to over one-third of his body, his wounds were sprayed with 23 million stem cells isolated from a tiny 2 x 2 sample of his own skin. Within five days of treatment, his chest and arms were already healed. Four days later, the patient was discharged from the hospital, said Mr. Bold.

These published analyses are especially encouraging to us because patients were successfully treated with the technology no matter what the source of the burn, concluded Mr. Bold.

Six Burn Causes: Patient Results and Photos Click here to see before-after photos

According to the Burns article authors, regardless of the burn type, cell spray showed quick healing (fast epithelialization), along with other benefits. "Cell-spray grafting is also especially suitable for hands and joint areas, where prolonged times to re-epithelization may significantly impact functionality and esthetic outcome," said the report.

Other findings in the article, following cell spray with the technology include:

Gas Explosion Patient

A gas explosion caused burns to the upper right arm and partial right chest area of a 43-year-old man who also suffered orthopedic injuries. "There was no evidence of hypertrophic (abnormalenlargementofanorgan) scarring throughout the prior burn area, and his only functional impairment ... was due to his wrist injury," concluded the report.

Chemical Explosion Burn

A 37-year-old patient suffered serious burns to his arms and hands as a result of a potassium nitrate explosion. The report observed the following outcome: "... the areas of autografts were noted to be almost indiscernible with the normal skin ... The patient maintained a full range of motion in all extremities without restriction."

Electrical Burn

After grabbing a live electrical wire a 35-year-old male received deep burns to the head, chest, abdomen, back, right hand and foot. Doctors indicated a full recovery to the affected areas in the article: ... all of the areas treated with cell spray grafting were noted as completely healed and re-epithelialized ... the patient had a functional range of motion in all extremities."

Gasoline Flame Burn

A gasoline flame injury to an 18-year-old male resulted in burns to the arms and legs. Forty-five million cells were obtained from the patient and used to spray the entire burn wound surface. "Wounds were completely healed by ... and there was no evidence of ... scarring or contractures, and the patient demonstrated a full range of motion in all extremities," the article said.

Hot Water Scalding

A hot water scalding injury covered a 43-year-old patients upper left arm, shoulder, back and torso. His post cell spray treatment provided the following results: "A 100% re-epithelialization was noted and the patient was discharged that day with instructions to apply Eucerin moisturizer to the wound ... the patient was also noted to have a full range of motion in his extremities, according to the article.

Hot Tar Scalding

Hot tar burned a 43-year-old mans right arm, right hand and midsection and within seven days of treatment the article concluded: all areas were noted to be healed and re-epithelialized and the patient was discharged.

The Burns article titled, Second-degree burns with six etiologies treated with autologous noncultured cell-spray grafting, by: Roger Esteban-Vives, Myung S. Choi, Matthew T. Young, Patrick Over, Jenny Ziembicki, Alain Corcos, and Jrg Gerlach, was published by Elsevier in the November 2016 issue of Burns (Nov;42(7):e99-e106. doi: 10.1016/j.burns.2016.02.020. Epub 2016 Aug 25).

Copies of the article are available to credentialed journalists upon request; please contact Elsevier's Newsroom at newsroom@elsevier.com or+31 20 485 2492.

Study authors, Dr. Roger Esteban-Vives and Dr. Jrg Gerlach currently have a financial interest in the SkinGun spray-grafting technology through payments from RenovaCare, Inc. Dr. Esteban-Vives, who currently Director of Cell Sciences at RenovaCare, Inc., was a postdoctoral fellow at the University of Pittsburgh when this work was conducted and did not have such financial interest at that time.

*RenovaCare products are currently in development.They are not available for sale in theUnited States. There is no assurance that the companys planned or filed submissions to the U.S. Food and Drug Administration, if any, will be accepted or cleared by the FDA.

AboutBurns

Burnsaims to foster the exchange of information among all engaged in preventing and treating the effects of burns. The journal focuses on clinical, scientific and social aspects of these injuries and covers the prevention of the injury, the epidemiology of such injuries and all aspects of treatment including development of new techniques and technologies and verification of existing ones. Regular features include clinical and scientific papers, state of the art reviews and descriptions of burn-care in practice.

About RenovaCare

RenovaCare, Inc. is developing first-of-its-kind autologous (self-donated) stem cell therapies for the regeneration of human organs. Its initial product under development targets the bodys largest organ, the skin. The companys flagship technology, the CellMist System, uses its patented SkinGun to spray a liquid suspension of a patients stem cells the CellMist Solution onto wounds. RenovaCare is developing its CellMist System as a promising new alternative for patients suffering from burns, chronic and acute wounds, and scars. In the US alone, this $45 billion market is greater than the spending on high-blood pressure management, cholesterol treatments, and back pain therapeutics.

For additional information, please call Drew Danielson at: 888-398-0202 or visit: http://renovacareinc.com

To receive future press releases via email, please visit: http://renovacareinc.com/investors/register/

Follow us on Twitterhttps://twitter.com/Renovacareincor follow us on Facebook https://www.facebook.com/renovacarercar

For answers to frequently asked questions, please visit our FAQs page: http://renovacareinc.com/investors/faqs/

Social Media Disclaimer

Investors and others should note that we announce material financial information to our investors using SEC filings and press releases. We use our website and social media to communicate with our subscribers, shareholders and the public about the company, RenovaCare, Inc. development, and other corporate matters that are in the public domain. At this time, the company will not post information on social media that could be deemed to be material information unless that information was distributed to public distribution channels first. We encourage investors, the media, and others interested in the company to review the information we post on the companys website and the social media channels listed below:

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* This list may be updated from time to time.

Legal Notice Regarding Forward-Looking Statements

No statement herein should be considered an offer or a solicitation of an offer for the purchase or sale of any securities. This release contains forward-looking statements that are based upon current expectations or beliefs, as well as a number of assumptions about future events. Although RenovaCare, Inc. (the Company) believes that the expectations reflected in the forward-looking statements and the assumptions upon which they are based are reasonable, it can give no assurance that such expectations and assumptions will prove to have been correct. Forward-looking statements, which involve assumptions and describe our future plans, strategies, and expectations, are generally identifiable by use of the words may, will, should, could, expect, anticipate, estimate, believe, intend, or project or the negative of these words or other variations on these words or comparable terminology. The reader is cautioned not to put undue reliance on these forward-looking statements, as these statements are subject to numerous factors and uncertainties, including but not limited to: the timing and success of clinical and preclinical studies of product candidates, the potential timing and success of the Companys product programs through their individual product development and regulatory approval processes, adverse economic conditions, intense competition, lack of meaningful research results, entry of new competitors and products, inadequate capital, unexpected costs and operating deficits, increases in general and administrative costs, termination of contracts or agreements, obsolescence of the Company's technologies, technical problems with the Company's research, price increases for supplies and components, litigation and administrative proceedings involving the Company, the possible acquisition of new businesses or technologies that result in operating losses or that do not perform as anticipated, unanticipated losses, the possible fluctuation and volatility of the Company's operating results, financial condition and stock price, losses incurred in litigating and settling cases, dilution in the Company's ownership of its business, adverse publicity and news coverage, inability to carry out research, development and commercialization plans, loss or retirement of key executives and research scientists, and other risks. There can be no assurance that further research and development will validate and support the results of our preliminary research and studies. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that the Company will be able to develop commercially viable products on the basis of its technologies. In addition, other factors that could cause actual results to differ materially are discussed in the Company's most recent Form 10-Q and Form 10-K filings with the Securities and Exchange Commission. These reports and filings may be inspected and copied at the Public Reference Room maintained by the U.S. Securities & Exchange Commission at 100 F Street, N.E., Washington, D.C. 20549. You can obtain information about operation of the Public Reference Room by calling the U.S. Securities & Exchange Commission at 1-800-SEC-0330. The U.S. Securities & Exchange Commission also maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the U.S. Securities & Exchange Commission athttp://www.sec.gov. The Company undertakes no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

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Outcomes of Burn Patients Treated with Cell Spray Technology ... - Business Wire (press release)

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An artist's impression of the reengineered cell that produces an anti-inflammatory drug when it encounters inflammation (Credit: Ella Marushchenko)

Combining two cellular-editing processes, researchers have developed cartilage that fights inflammation. The scientists hope that the breakthrough could eventually lead to localized injections that combat arthritis or perhaps a vaccine that would eliminate the condition altogether.

Like many of the biology breakthroughs happening today, the WU researchers started with stem cells. To be more accurate, they actually started with skin cells from the tails of mice and converted them into stem cells. They then used a gene-editing technique called CRISPR to remove a gene involved in inflammation and replace it with one that releases an anti-inflammatory drug. The resulting cells are known as SMART cells, which stands for Stem cells Modified for Autonomous Regenerative Therapy.

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"Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed," said Farshid Guilak, the senior author of a paper about the work and a professor of orthopedic surgery at Washington University School of Medicine. "To do this, we needed to create a 'smart' cell."

As part of the current fight against arthritis, there are several drugs that work to eliminate an inflammatory molecule called tumor necrosis factor-alpha (TNF-alpha). The issue with such drugs, however, is that they work throughout the entire body, rather than only at the site of inflammation, and can have an impact on the body's overall immune system.

To change this dynamic, the researchers replaced the gene that expresses TNF-alpha with one that inhibits it by releasing a drug, basically converting the cells from those that create inflammation to those that fight it. "We hijacked an inflammatory pathway to create cells that produced a protective drug," said Jonathan Brunger, a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco. They then coaxed these cells to grow into cartilage in the lab which, they found, was successful in combating inflammation.

The hope is that injecting the cells into areas afflicted by arthritis, the new anti-inflammatory cartilage could replace the old cartilage. This would effectively create a vaccine against the condition, as the newly engineered cells would only release the anti-inflammatory drug when inflammation is present such as during an arthritic flare-up and turn off the release of the drug when the flare subsides.

Additionally, the researchers also engineered the new cells to light up when they responded to inflammation so that they could track their response in the body. The cells are now being tested in mice with rheumatoid arthritis and other inflammatory disorders and the researchers think that the method of combining stem cells with CRISPR could help fight other diseases as well.

"We believe this strategy also may work for other systems that depend on a feedback loop," said Guilak. "In diabetes, for example, it's possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders."

The paper is published in the journal Stem Cell Reports.

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SMART cells open door to arthritis vaccine - New Atlas

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Current CRISPR Patent Dispute, Explained CALIFORNIA They invented CRISPR-Cas9, a gene editing tool that uses a protein found in Streptococcus bacteria to chop up and rearrange viral DNA with precision. The implications of the technology were immediately apparent, astonishing, and perhaps just a wee bit ... and more »

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Current CRISPR Patent Dispute, Explained - CALIFORNIA

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Boston Business Journal

CEOs of top gene-editing firms got huge compensation hikes last year Boston Business Journal It's no secret that the burgeoning field of gene-editing a method of cutting out and replacing part of a gene has generated serious buzz in the biotech world lately. New scientific tools like CRISPR/Cas9 have the potential to revolutionize the ... CRISPR Therapeutics to Present at the 42nd Annual Deutsche Bank Health Care ConferenceGlobeNewswire (press release) Intellia (NTLA), CRISPR Therapeutics (CRSP) Receive U.S. Patent for CRISPR/Cas9 Ribonucleoprotein ComplexesStreetInsider.com Intellia Therapeutics and CRISPR Therapeutics Announce U.S. ...Yahoo Finance Texas Tribune -The Cerbat Gem -Sports Perspectives all 27 news articles »

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CEOs of top gene-editing firms got huge compensation hikes last year - Boston Business Journal

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For the first time, scientists have demonstrated high efficiency multiplex gene editing in plants.

Asian Scientist Newsroom | April 28, 2017 | In the Lab

AsianScientist (Apr. 28, 2017) - Using Cpf1 instead of the more familiar Cas9, researchers from China have developed an easier way to edit multiple genes with CRISPR technology, demonstrating their method in rice. Their findings have been published in Molecular Plant.

Multiplex gene editing provides a powerful tool for targeting members of multigene families. Although previous studies have shown that multiplex gene editing in plants is possible with CRISPR-Cas9, the Cas9 system requires large constructs to express multiple sgRNA cassettes, which are more laborious to construct and could cause unstability and reduce transformation efficiency.

Cpf1 is a dual nuclease that not only cleaves target DNA but also processes its own CRISPR RNA. A study led by Professor Zhu Jiankangs lab at Institute of Plant Physiology and Ecology of Chinese Academy of Sciences tested FnCpf1 and LbCpf1 for single and multiplex gene editing in rice.

Researchers found that both FnCpf1 and LbCpf1 with their own mature direct repeats induce mutations in transgenic plants. The LbCpf1 system gave higher editing efficiency in all six tested target sites.

Importantly, FnCpf1 and LbCpf1 also showed robust activity in multiplex gene editing when expressed together with a single CRISPR array. It has been proved that FnCpf1 and LbCpf1 are functional when the direct repeat sequences of their CRISPR arrays are exchanged.

This study demonstrated for the first time the feasibility of high efficiency multiplex gene editing in plants using engineered CRISPR-Cpf1 with a simple short DR-guide array, which significantly simplifies multiplex gene editing in plants.

The article can be found at: Wang et al. (2017) Multiplex Gene Editing in Rice Using the CRISPR-Cpf1 System.

Source: Chinese Academy of Sciences; Photo: Shutterstock. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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CRISPR Used To Modify Multiple Genes In Rice - Asian Scientist Magazine

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Sarasota, FL (SBWIRE) 04/25/2017 Zion Market Research, the market research group announced the analysis report titled Male Hypogonadism Market: Global Industry Analysis, Size, Share, Growth, Trends, and Forecasts 20162024

Global Male Hypogonadism Market: Overview

Male hypogonadism is a medical condition, wherein the testes fail to generate enough testosterone which leads to incomplete development or delayed puberty. The condition is related to the development of breast tissues, impaired development of muscle mass, lack of deepening of the voice, and impaired body hair growth.

Global Male Hypogonadism Market: Segmentation

The male hypogonadism market is globally segmented into therapy, drug delivery, and type. On the basis of therapy, the market is segregated into testosterone replacement therapy and gonadotropin-releasing hormones therapy. The gonadotropin-releasing hormones therapy is further sub-divided into luteinizing hormone (LH), human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH). Based on the drug delivery, the market is categorized into injectables, topical gels, transdermal patches, and others. Depending on the type, the market is divided into Kallmann syndrome, Klinefelters syndrome, pituitary disorders, and others.

Request Free Sample Report @ https://www.zionmarketresearch.com/sample/male-hypogonadism-market

Global Male Hypogonadism Market: Growth Factors

The key factor that is driving the male hypogonadism market includes increasing cases of testosterone deficiency among men, increasing awareness among people about hypogonadism treatment owing to awareness drives that are organized by several governments across the world, and increasing infertility rates. The high risk of hypogonadism among the aged population with obesity and diabetes and escalating cases of chronic disorders among the geriatrics are further boosting the markets growth. On the other hand, factors such as high side effects of testosterone products challenge the growth of the market. The market players are focusing on research and development activities to introduce newer products with less or negligible side effects and better results. Technological advancements are anticipated to extend new opportunities to the markets growth.

Global Male Hypogonadism Market: Regional Analysis

The male hypogonadism market can be segmented into regions such as North America, Asia-Pacific, Europe, Latin America, and the Middle East and Africa. North America dominates the market owing to the increase in the number of individuals that are suffering from the primary and secondary conditions of hypogonadism, and the rising awareness among the people about treatment. Other factors that contribute to this growth are the presence of unconventional health care infrastructure and growing popularity of the technologically advanced products which will offer new opportunities to the top market players in this market. The region is strongly followed by Europe. Asia-Pacific region is expected to offer productive opportunities to this market owing to the modernization of the healthcare infrastructure in the developing economies of India and China and the growing awareness about the treatment for the condition. In Asia Pacific, there is a rise in the number of people that suffer from hypogonadism and infertility rates coupled with the rise in the geriatric population base having obesity and diabetes are triggering the growth of the market.

Global Male Hypogonadism Market: Competitive Players

Some of the key market players that are involved in the male hypogonadism market include Astrazeneca Plc., Merck & Co. Inc., Laboratories Genevrier, Allergan Plc., Endo International Plc., Ferring, AbbVie Inc., Eli Lilly and Company Ltd., Finox Biotech, Teva Pharmaceutical Industries Ltd., Bayer AG, and IBSA Institut Biochimque.

Request Report TOC (Table of Contents) @ https://www.zionmarketresearch.com/toc/male-hypogonadism-market

Global Male Hypogonadism Market: Regional Segment Analysis

North America U.S. Europe UK France Germany Asia Pacific China Japan India Latin America Brazil The Middle East and Africa

What Reports Provides

Full in-depth analysis of the parent market Important changes in market dynamics Segmentation details of the market Former, on-going, and projected market analysis in terms of volume and value Assessment of niche industry developments Market share analysis Key strategies of major players Emerging segments and regional markets Testimonials to companies in order to fortify their foothold in the market.

Browse detail report @ https://www.zionmarketresearch.com/report/male-hypogonadism-market

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Global Male Hypogonadism Market, 20162024: Type. Size, Share, Trends & Forecast Report - satPRnews (press release)

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Researchers have showncertain cardiac glycosides can reduce hepatocyte production of aprecursor of LDL cholesterol.

Familial hypercholesterolaemia (FH) is a rare genetic disease that affects the production of functioning low-density lipoprotein (LDL) receptors in the liver. When patients have mutations in both copies of the LDL receptor gene, they do not respond to statins and have limited pharmaceutical treatment options available because of a lack of accurate disease models.

Reporting in Cell Stem Cell on 6 April 2017[1], researchers used FH human hepatocytes derived from induced pluripotent stem cells to screen for existing drugs that might lower apolipoprotein B (apoB) a precursor of LDL cholesterol.

The team found that all nine cardiac glycosides in their drug library reduced levels of apoB in the hepatocytes. In an analysis of historical patient data, the researchers found a reduction in serum LDL-C comparable to that seen with statins in patients taking cardiac glycosides.

The researchers say the results demonstrate the potential of their stem-cell based approach for identifying new treatment candidates for inherited liver diseases.

Citation: Clinical Pharmacist, CP April 2017 online, online | DOI: 10.1211/CP.2017.20202623

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Stem-cell screening finds statin alternative for hypercholesterolaemia - The Pharmaceutical Journal

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April 26, 2017 A mouse tibia that has been rendered transparent with Bone CLARITY. Stem cells appear distributed throughout the bone in red. The ability to see bone stem cell behavior is crucial for testing new osteoporosis treatments. Credit: Science Translational Medicine, Greenbaum, Chan, et al; Gradinaru laboratory/Caltech

Ten years ago, the bones currently in your body did not actually exist. Like skin, bone is constantly renewing itself, shedding old tissue and growing it anew from stem cells in the bone marrow. Now, a new technique developed at Caltech can render intact bones transparent, allowing researchers to observe these stem cells within their environment. The method is a breakthrough for testing new drugs to combat diseases like osteoporosis.

The research was done in the laboratory of Viviana Gradinaru (BS '05), assistant professor of biology and biological engineering and a Heritage Medical Research Institute Investigator. It appears in a paper in the April 26 issue of Science Translational Medicine.

In healthy bone, a delicate balance exists between the cells that build bone mass and the cells that break down old bone in a continual remodeling cycle. This process is partially controlled by stem cells in bone marrow, called osteoprogenitors, that develop into osteoblasts or osteocytes, which regulate and maintain the skeleton. To better understand diseases like osteoporosis, which occurs when loss of bone mass leads to a high risk of fractures, it is crucial to study the behavior of stem cells in bone marrow. However, this population is rare and not distributed uniformly throughout the bone.

"Because of the sparsity of the stem cell population in the bone, it is challenging to extrapolate their numbers and positions from just a few slices of bone," says Alon Greenbaum, postdoctoral scholar in biology and biological engineering and co-first author on the paper. "Additionally, slicing into bone causes deterioration and loses the complex and three-dimensional environment of the stem cell inside the bone. So there is a need to see inside intact tissue."

To do this, the team built upon a technique called CLARITY, originally developed for clearing brain tissue during Gradinaru's postgraduate work at Stanford University. CLARITY renders soft tissues, such as brain, transparent by removing opaque molecules called lipids from cells while also providing structural support by an infusion of a clear hydrogel mesh. Gradinaru's group at Caltech later expanded the method to make all of the soft tissue in a mouse's body transparent. The team next set out to develop a way to clear hard tissues, like the bone that makes up our skeleton.

In the work described in the new paper, the team began with bones taken from postmortem transgenic mice. These mice were genetically engineered to have their stem cells fluoresce red so that they could be easily imaged. The team examined the femur and tibia, as well as the bones of the vertebral column; each of the samples was about a few centimeters long. First, the researchers removed calcium from the bones: calcium contributes to opacity, and bone tissue has a much higher amount of calcium than soft tissues. Next, because lipids also provide tissues with structure, the team infused the bone with a hydrogel that locked cellular components like proteins and nucleic acids into place and preserved the architecture of the samples. Finally, a gentle detergent was flowed throughout the bone to wash away the lipids, leaving the bone transparent to the eye. For imaging the cleared bones, the team built a custom light- sheet microscope for fast and high-resolution visualization that would not damage the fluorescent signal. The cleared bones revealed a constellation of red fluorescing stem cells inside.

The group collaborated with researchers at the biotechnology company Amgen to use the method, named Bone CLARITY, to test a new drug developed for treating osteoporosis, which affects millions of Americans per year.

"Our collaborators at Amgen sent us a new therapeutic that increases bone mass," says Ken Chan, graduate student and co-first author of the paper. "However, the effect of these therapeutics on the stem cell population was unclear. We reasoned that they might be increasing the proliferation of stem cells." To test this, the researchers gave one group of mice the treatment and, using Bone CLARITY, compared their vertebral columns with bones from a control group of animals that did not get the drug. "We saw that indeed there was an increase in stem cells with this drug," he says. "Monitoring stem cell responses to these kinds of drugs is crucial because early increases in proliferation are expected while new bone is being built, but long-term proliferation can lead to cancer."

The technique has promising applications for understanding how bones interact with the rest of the body.

"Biologists are beginning to discover that bones are not just structural supports," says Gradinaru, who also serves as the director of the Center for Molecular and Cellular Neuroscience at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. "For example, hormones from bone send the brain signals to regulate appetite, and studying the interface between the skull and the brain is a vital part of neuroscience. It is our hope that Bone CLARITY will help break new ground in understanding the inner workings of these important organs."

The paper is titled "Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow."

Explore further: Growing new bone for more effective injury repair

More information: Alon Greenbaum et al, Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow, Science Translational Medicine (2017). DOI: 10.1126/scitranslmed.aah6518

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Transparent bones enable researchers to observe the stem cells inside - Medical Xpress

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It's based on experimental research that suggests stem cells extracted from the pulp of these teeth might someday regrow a lost adult tooth or offer other regenerative medicine benefits -- some potentially life-saving.

"So I'll try not to get emotional here, but my husband was diagnosed with acute myeloid leukemia in 2011," said Bassetto, of Naperville, Illinois, head of a sales team at a software company.

In 2012, her husband, James, had a stem cell transplant to restore his bone marrow and renew his blood.

"He was very fortunate. He was one of six kids, and his brother was a perfect match," she said. She noted that her two children, Madeline, 23, and Alex, 19, may not be so lucky if they develop health problems, since they have only each other; the chance of two siblings being a perfect stem cell match is only 25%.

Unfortunately, her husband's stem cell transplant was not successful. He developed graft-versus-host disease, where his brother's donated stem cells attacked his own cells, and he died shortly afterward.

However, she says, the transplant had given him a chance at a longer life.

Last year, when her son saw a dentist for wisdom tooth pain, a brochure for dental stem cell storage caught Bassetto's eye and struck a chord.

"I know stem cells have tremendous health benefits in fighting disease, and there's a lot ways they're used today," she said. "Had my husband had his own cells, potentially, his treatment could have been more successful."

Medical breakthroughs happen all the time, said Bassetto. "Who knows what potential there is 20 years, 40 years down the road, when my son is an adult or an aging adult?

"Almost like a life insurance policy, is how I viewed it," she said.

Some scientists see storing teeth as a worthwhile investment, but others say it's a dead end.

"Research is still mostly in the experimental (preclinical) phase," said Ben Scheven, senior lecturer in oral cell biology in the school of dentistry at the University of Birmingham. Still, he said, "dental stem cells may provide an advantageous cell therapy for repair and regeneration of tissues," someday becoming the basis for reconstructing bone tissue, retinas and even optic neurons.

Dr. Pamela Robey, chief of the craniofacial and skeletal diseases branch of the National Institute of Dental and Craniofacial Research, acknowledges the "promising" studies, but she has a different take on the importance of the cells.

"There are studies with dental pulp cells being used to treat neurological disorders and problems in the eye and other things," Robey said. The research is based on the idea that these cells "secrete factors that encourage local cells to begin the repair process."

"The problem is, these studies have really not been that rigorous," she said, adding that many have been done only in animals and so provide "slim" evidence of benefits. "The science needs a lot more work."

Robey would know. Her laboratory discovered dental stem cells in 2003.

"My fellows, Songtao Shi and Stan Gronthos, did the work in my lab," Robey said. "Songtao Shi is a dentist, and basically he observed that, when you get a cavity, you get what's called 'reparative dentin.' In other words, the tooth is trying to protect itself from that cavity, so it makes a little bit of dentin to kind of plug the hole, so to speak."

Dentin is the innermost hard layer of tooth that lies beneath the enamel. Underneath the dentin is a soft tissue known as pulp, which contains the nerve tissue and blood supply.

Observing dentin perform reparative work, Shi hypothesized that this must mean there's a stem cell within the tooth that's able to activate and make dentin. So if you wanted to grow an adult tooth instead of getting an implant, knowing how to make dentin would be the start of the process, explained Robey.

Pursuing this idea, Shi, Gronthos and the team conducted their first study with wisdom teeth. They discovered that pulp cells in these third molars did indeed make dentin, but the cells found in baby teeth, called SHED (stem cells from human exfoliated deciduous teeth), had slightly different properties.

"The SHED cells seem to make not only dentin but also something that is similar to bone," Robey said. This "dentin osteogenic material" is a little like bone and a little like dentin -- "unusual stuff," she said.

There is a meticulous process for extracting stem cells from the pulp.

"We very carefully remove any soft tissue that's adhering to the tooth. We treat it with disinfectant, because the mouth is not really that clean," Robey said, laughing.

Scientists then use a dental drill to pass the enamel and dentin -- "kind of like opening up a clam," said Robey -- to get to the pulp. "We take the pulp out, and we digest it with an enzyme to release the cells from the matrix of the pulp, and then we put the cells into culture and grow them."

According to Laning, even very small amounts of dental pulp are capable of producing many hundreds of millions of structural stem cells.

Harvesting dental stem cells is not a matter of waiting for the tooth to fall out and then quickly calling your dentist. When a baby tooth falls out, the viability of the pulp is limited if it's not preserved in the proper solution.

American Academy of Pediatric Dentistry President Dr. Jade Miller explained that "it's critical that the nerve tissue in that pulp tissue, the nerve supply and blood supply, still remain intact and alive." Typically, the best baby teeth to harvest are the upper front six or lower front six -- incisors and cuspids, he said.

For a child between 5 and 8 years of age, it's best to extract the tooth when there's about one-third of the root remaining, Miller said: "It really requires some planning, and so parents need to make this decision early on and be prepared and speak with their pediatric dentist about that."

Bassetto found the process easy. All it involved was a phone call to the company recommended by her dentist.

"They offer a service where they grow the cells and save those and also keep the pulp of the tooth without growing cells from it," she said. "I opted for both." From there, she said, the dentist shipped the extracted teeth overnight in a special package.

Bassetto said she paid less than $2,000 upfront, and now $10 a month for continued storage.

So is banking teeth something parents should be doing?

In a policy statement, the American Academy of Pediatric Dentistry "encourages dentists to follow future evidence-based literature in order to educate parents about the collection, storage, viability, and use of dental stem cells with respect to autologous regenerative therapies."

"Right now, I don't think it is a logical thing to do. That's my personal opinion," said Robey of the National Institute of Dental and Craniofacial Research. As of today, "we don't have methods for creating a viable tooth. I think they're coming down the pike, but it's not around the corner."

Science also does not yet support using dental pulp stem cells for other purposes.

"That's not to say that in the future, somebody could come up with a method that would make them very beneficial," Robey said.

Still, she observed, if science made it possible to grow natural teeth from stem cells and you were in a car accident, for example, and lost your two front teeth, you'd probably be "very happy to give up a third molar to use the cells in the molar to create new teeth." Third molars are fairly expendable, she said.

Plus, Robey explained, it may not be necessary to bank teeth: Another type of stem cell, known as induced pluripotent stem cells, can be programmed into almost any cell type.

"It's quite a different story than banking umbilical cord blood, which we do know contains stem cells that re-create blood," Robey said.

"So cord blood banking -- and now we have a national cord blood bank as opposed to private clinics -- so there's a real rationale for banking cord blood, whereas the rationale for banking baby teeth is far less clear," Robey said.

And there's no guarantee that your long-cryopreserved teeth or cells will be viable in the future. Banking teeth requires proper care and oversight on the part of cryopreservation companies, she said. "I think that that's a big question mark. If you wanted to get your baby teeth back, how would they handle that? How would they take the tooth out of storage and isolate viable cells?"

Provia's Laning, who has "successfully thawed cells that have been frozen for more than 30 years," dismissed such ideas.

"Cryopreservation technology is not the problem here," he said. "Stem cells from bone marrow and other sources have been frozen for future clinical use in transplants for more than 50 years. Similarly, cord blood has a track record of almost 40 years." The technology for long-term cryopreservation has been refined over the years without any substantial changes, he said.

Despite issues and doubts, Miller, of the pediatric dentistry academy, said parents still need to consider banking baby teeth.

A grandparent, he is making the decision for his own family.

"It's really at its infancy, much of this research," he said. "There's a very strong chance there's going to be utilization for these stem cells, and they could be life-saving."

He believes that saving baby teeth could benefit not only his grandchildren but also their older siblings and various other family members if their health goes awry and a stem cell treatment is needed.

"The science is strong enough to show it's not science fiction," Miller said. "There's going to be a significant application, and I want to give my grandkids the opportunity to have those options."

Aside from cost, Miller said there are other considerations: "Is this company going to be around in 30, 40 years?" he asked. "That's not an easy thing to figure out."

Having taken the leap, Bassetto doesn't worry.

"In terms of viability, you know, if something were to happen with the company, you could always get what's stored and move it elsewhere, so I felt I was protected that way," she said. She feels "pretty confident" with her decision and plans to store her grandchildren's baby teeth.

Still, she concedes that her circumstances may be rare.

"Not everybody's going to be touched by some kind of disease where it just hits home," Bassetto said. "For me, that made it a no-brainer."

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Are baby, wisdom teeth the next wave in stem cell treatment? - CNN

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Using video microscopy in the living mouse lung, UC San Francisco scientists have revealed that the lungs play a previously unrecognized role in blood production. As reported online March 22, 2017, inNature, the researchers found that the lungs produced more than half of the platelets blood components required for the clotting that stanches bleeding in the mouse circulation.

In another surprise finding, the scientists also identified a previously unknown pool of blood stem cells capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted.

This finding definitely suggests a more sophisticated view of the lungs that theyre not just for respiration but also a key partner in formation of crucial aspects of the blood, said pulmonologistMark R. Looney, a professor of medicine and of laboratory medicine at UCSF and the new papers senior author. What weve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.

The findings could have majorimplications for understanding human diseases in which patients suffer from low platelet counts, or thrombocytopenia, which afflicts millions of people and increases the risk of dangerous uncontrolled bleeding. The findings also raise questions about how blood stem cells residing in the lungs may affect the recipients of lung transplants.

The new study was made possible by a refinement of a technique known as two-photon intravital imaging recently developed by Looney and co-authorMatthew F. Krummel, a UCSF professor of pathology. This imaging approach allowed the researchers to perform the extremely delicate task of visualizing the behavior of individual cells within the tiny blood vessels of a living mouse lung.

Looney and his team were using this technique to examine interactions between the immune system and circulating platelets in the lungs, using a mouse strain engineered so that platelets emit bright green fluorescence, when they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up, saidEmma Lefranais, a postdoctoral researcher in Looneys lab and co-first author on the new paper.

More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature, suggesting that more than half of a mouses total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed. Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature estimated at 1 million per mouse lung.

The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:

First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.

Its fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets, said Guadalupe Ortiz-Muoz, a postdoctoral researcher in the Looney lab and the papers other co-first author. Its possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we dont yet know about.

"Its possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we dont yet know about."

Guadalupe Ortiz-Muoz, postdoctoral researcher in the Mark Looney Lab

In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouses low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.

Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.

To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia, said Looney, who is also an attending physician on UCSFs pulmonary consult service and intensive care units.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Looney said. The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation, said pulmonologist Guy A. Zimmerman, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of the new study forNature. The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.

The observation that blood stem cells and progenitors seem to travel back and forth freely between the lung and bone marrow lends support to a growing sense among researchers that stem cells may be much more active than previously appreciated, Looney said. Were seeing more and more that the stem cells that produce the blood dont just live in one place but travel around through the blood stream. Perhaps studying abroad in different organs is a normal part of stem cell education.

The study was supported the UCSF Nina Ireland Program in Lung Health, the UCSF Program for Breakthrough Biomedical Research, and the National Heart, Lung, and Blood Institute (NHLBI), a division of the National Institutes of Health (HL092471, HL107386 and HL130324).

It has been known for decades that the lung can be a site of platelet production, but this study amplifies this idea by demonstrating that the murine lung is a major participant in the process, said Traci Mondoro,project officer at the Translational Blood Science and Resources Branch of the NHLBI. Dr. Looney and his team have disrupted some traditional ideas about the pulmonary role in platelet-related hematopoiesis, paving the way for further scientific exploration of this integrated biology.

Additional authors included Axelle Caudrillier,Beat Mallavia,Fengchun Liu, Emily E. Thornton,Mark B. Headley,Tovo David, Shaun R. Coughlin, Andrew D. Leavitt, David M. Sayah, of UCLA; and Emmanuelle Passegu,a former UCSF faculty member who is now director of the Columbia Stem Cell Initiative at Columbia University Medical Center.

Cover photo:iStock/choja

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Surprising new role for lungs: Making blood - University of California

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A bone marrow drive for James Christopher Allums, 21, and his sister Elizabeth, 3, is Monday, May 1 at locations throughout northeast Louisiana.

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The News Star 11:33 a.m. CT April 26, 2017

University of Louisiana Monroe(Photo: Courtesy image)

A bone marrow drive for James Christopher Allums, 21, and his sister Elizabeth, 3, is Monday, May 1 at locations throughout northeast Louisiana.

University of Louisiana Monroe Medical Laboratory Science faculty and students are helping organize the drive. The drive on campus is 9 a.m.-5 p.m. in the SUB and Quad.

May 1 is National Fanconi Anemia Day. James Christopher and Elizabeth suffer from this disease, which is fatal without a bone marrow or stem cell transplant. They are the children of Chris and Ellen Allums.

Melanie Chapman, assistant professor to the School of Health Professions, said, "This is a wonderful opportunity for ULM Warhawks to fly high by working together and setting aside our busy agendas to give two great kids, and possibly others, the chance to live out their years. I am privileged to be a part of ULM and this community effort."

Bone marrow drive locations:

Times vary and new locations may be added. For information, check Facebook The Friends of James Christopher and Elizabeth Allums or visit caringbridge.org and search James Christopher Allums .

MORE NEWS;The Fabulous Equinox Orchestra takes the stage at ULM Friday

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Bone marrow drive for Allums siblings at ULM, other locations - Monroe News Star

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Cancerous cells in a skin tumor become locked in an abnormal state as a result of the activation of a gene-regulating element (green).

Like an image in a broken mirror, a tumor is a distorted likeness of a wound. Scientists have long seen parallels between the two, such as the formation of new blood vessels, which occurs as part of both wound healing and malignancy.

Research at The Rockefeller University offers new insights about what the two processes have in commonand how they differat the molecular level. The findings, described April 20 in Cell, may aid in the development of new therapies for cancer.

Losing identity

At the core of both malignancy and tissue mending are stem cells, which multiply to produce new tissue to fill the breach or enlarge the tumor. To see how stem cells behave in these scenarios, a team led by scientists in Elaine Fuchss lab compared two distinct types found within mouse skin.

One set of stem cells, at the base of the follicle, differentiates to form the hair shaft; while another set produces new skin cells. Under normal conditions, these two cell populations are physically distinct, producing only their respective tissue, nothing else.

But when Yejing Ge, a postdoc in the Fuchs lab, looked closely at gene activity in skin tumors, she found a remarkable convergence: The follicle stem cells expressed genes normally reserved for skin stem cells, and vice versa. Around wounds, the researchers documented the same blurring between the sets of stem cells.

Master switches

Two of the identity-related genes stood out. They code for so-called master regulators, molecules that play a dominant role in determining what type of tissue a stem cell will ultimately producein this case, hair follicle or skin. The researchers suspect that stress signals from the tissue surrounding the damage or malignancy kick off a cycle that feeds off itself by enabling the master regulators to make more of themselves.

Access to DNA is the key. To go to work, master regulators bind to certain regions of DNA and so initiate dramatic changes in gene expression. The researchers found evidence that stress signals open up new regions of DNA, making them more accessible to gene activation. By binding in these newly available spots, master regulators elevate the expression of identity-related genes, including the genes that encode the master regulators themselves.

Locked in

While wounds heal, cancer can grow indefinitely. The researchers discovered that while stress signals eventually wane in healing wounds, they can persist in cancerand with prolonged stress signaling, another region of DNA opens up to kick off a separate round of cancer-specific changes.

Tumors have been described as wounds that never heal, and now we have identified specific regulatory elements that, when activated, keep tumor cells locked into a blurred identity, Ge says.

The scientists hope this discovery could lead to precise treatments for cancer that cause less collateral damage than conventional chemotherapy. We are currently testing the specificity of these cancer regulatory elements in human cells for their possible use in therapies aimed at killing the tumor cells and leaving the healthy tissue cells unharmed, Fuchs says.

Elaine Fuchs is the Rebecca C. Lancefield Professor, head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, and a Howard Hughes Medical Institute investigator.

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A mechanism shared by healing wounds and growing tumors - The Rockefeller University Newswire

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A New Type of Stem Cell

While much has been gleaned about the power of stem cells over the last few decades, researchers from the Salk Institute and Peking Universityin China recently found out theres plenty left to discover and invent. Nature, it seems, will always keep you guessing.

In a study published in the journal Cell, the team of researchers revealed they had succeeded in creating a new kind of stem cell thats capable of becoming any type of cell in the human body. Extended pluripotent stem cells or EPS cells are similar to induced pluripotent stem cells(iPS cells), which were invented in 2006.

The key difference between the two is that iPS cells are made from skin cells (called fibroblasts) and EPS cells are made from a combination of skin cells and embryonic stem cells. iPS cells are the hallmark of stem cell research and can be programmed to become any cell in the human body hence the pluripotent part of their name. EPS cells, too, can give rise to any type of cell in the human body, but they can also do something very different something unprecedented, actually: they can create the tissues needed to nourish and grow an embryo.

The discovery of EPS cells provides a potential opportunity for developing a universal method to establish stem cells that have extended developmental potency in mammals, says Jun Wu, one of the studys authors and senior scientist at the Salk Institute, in the organizations news release.

When a human or any mammalian egg gets fertilized, the cells divide up into two task forces: one set is responsible for creating the embryo, and the other set creates the placenta and other supportive tissues needed for the embryo to survive (called extra-embryonic tissues). This happens very early in the reproductive process so early, in fact, that researchers have had a very hard time recreating it in a lab setting.

By culturing and studying both types of cells in action, researchers would not only be able to understand the mechanism that drives it, but hopefully could shed some light on what happens when things go wrong, like in the case of miscarriage.

The researchers at the Salk Institute managed to form a chemical cocktail of four chemicals and a type of growth factor that created a stable environment in which they could culture both types of cells in an immature state. They could then harness the two types of cells for their respective abilities.

What they discovered was that not only were these cells extremely useful for creating chimeras (where two types of animal cells or human and animal cells are mixed to form something new), but were also technically capable of creating and sustaining an entire embryo.At least in theory: while they were able to sustain both human and mouse cells, the ethical considerations of creating a human embryo this way have prevented them from attempting it.

That being said, theres no shortage of applications for this type of stem cell: researchers will be able to use them to model diseases, regenerate tissue, create and trial drug therapies, and study in depth early reproductive processes like implantation. Human-animal chimeras may also help engineer organs for transplant or, you know, give rise to the next superhero.

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Researchers Invent Stem Cell Capable of Becoming an Entire Embryo - Futurism

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(EnviroNews World News) Kobe, Japan For more than two million Americans, straight lines may look wavy and the vision in the center of their eye may slowly disappear. Its called age-related macular degeneration (AMD), and there is no cure. But that may change soon.

A surgical team at Kobe City Medical Center General Hospital in Japan recently injected 250,000 retinal pigment epithelial (RPE) cells into the right eye of a man in his 60s. The cells were derived from donor stem cells stored at Kyoto University. It marked the first time that retinal cells derived from a donors skin have been implanted in a patients eye. The skin cells had been reprogrammed into induced pluripotent stem cells (iPS), which can be grown into most cell types in the body.

The procedure is part of a safety study authorized by Japans Ministry of Health that will involve five patients. Each will be followed closely for one year and continue to receive follow-up exams for three additional years. Project leader Dr. Masayo Takahashi at Riken, a research institution that is part of the study, told the Japan Times, A key challenge in this case is to control rejection. We need to carefully continue treatment.

A previous procedure on a different patient in 2014 used stem cells from the individuals own skin. Two years later, the patient reported showing some improvement in eyesight. But the procedure cost $900,000, leading the study team to move forward using donor cells. They expect the costs to come down to less than $200,000.

Among people over 50 in developed countries, AMD is the leading cause of vision loss. According to the National Eye Institute, 14 percent of white Americans age 80 or older will suffer some form of AMD. The condition is almost three times more common among white adults than among people of color. Women of all races comprise 65 percent of AMD cases.

The lack of a cure has led some to try unproven treatments. Three elderly women lost their sight after paying $5,000 each for a stem cell procedure at a private clinic in Florida. Clinic staff used liposuction to remove fat from the womens bellies. They then extracted stem cells from the fat, which were injected into both eyes of each patient in the same procedure, resulting in vision loss in both eyes. Two of the three victims agreed to a lawsuit settlement with the company that owned the clinic.

Stem cell therapy is still at an early stage. As of January 2016, 10 clinical uses have been approved around the world, all using adult stem cells. These include some forms of leukemia and bone marrow disease, Hodgkin and non-Hodgkin lymphoma and some rare inherited disorders including sickle cell anemia. Stem cell transplants are now often used to treat multiple myeloma, which strikes more than 24,000 people a year in the U.S.

Clinical trials to treat type 1 diabetes, Parkinsons disease, stroke, brain tumors and other conditions are being conducted. The first patient in a nationwide clinical study to receive stem cell therapy for heart failure recently underwent the procedure at the University of Wisconsin School of Medicine and Public Health. An experimental treatment at Keck Medical Center of USC last year on a paralyzed patient restored the 21-year-old mans use of his arms and hands. Harvard scientists see stem cell biology as a path to counter aging and extend human lifespans. But the International Society for Stem Cell Research warns that there are many challenges ahead before these treatments are proven safe and effective.

The U.S. Food and Drug Administration (FDA) regulates stem cells to ensure that they are safe and effective for their intended use. But, that doesnt stop some clinics from preying on worried patients. The FDA warns on its website that the hope that patients have for cures not yet available may leave them vulnerable to unscrupulous providers of stem cell treatments that are illegal and potentially harmful.

While there is yet no magic cure for AMD, the Japan study and others may one day lead there. The Harvard Stem Cell Institute (HSCI) in Boston is currently researching retina stem cell transplants. One approach uses gene therapy to generate a molecule that preserves healthy vision. Another involves Muller cells, which give fish the ability to repair an injured retina.

But these therapies are far off. We are at about the halfway mark, but there is still a precipitous path ahead of us, Takahashi said.

More here:
World's 1st Stem Cell Transplant from Donor to Man's Eye Shows Promise of Restoring Sight - EnviroNews (registration) (blog)

Recommendation and review posted by simmons

Clustered regularly interspaced short palindromic repeats (CRISPR, pronounced crisper[2]) are segments of prokaryotic DNA containing short, repetitive base sequences. These play a key role in a bacterial defence system,[3] and form the basis of a genome editing technology known as CRISPR-Cas9 that allows permanent modification of genes within organisms.[4] In a palindromic repeat, the sequence of nucleotides is the same in both directions. Each repetition is followed by short segments of spacer DNA from previous exposures to foreign DNA (e.g., a virus or plasmid).[5] Small clusters of cas (CRISPR-associated system) genes are located next to CRISPR sequences.

The CRISPR/Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements such as those present within plasmids and phages[6][7][8] that provides a form of acquired immunity. RNA harboring the spacer sequence helps Cas proteins recognize and cut exogenous DNA. Other RNA-guided Cas proteins cut foreign RNA.[9] CRISPRs are found in approximately 40% of sequenced bacterial genomes and 90% of sequenced archaea.[10][note 1]

A simple version of the CRISPR/Cas system, CRISPR/Cas9, has been modified to edit genomes. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added.[11][12][13] The Cas9-gRNA complex corresponds with the CAS III crRNA complex in the above diagram.

CRISPR/Cas genome editing techniques have many potential applications, including medicine and crop seed enhancement. The use of CRISPR/Cas9-gRNA complex for genome editing[14][15] was the AAAS's choice for breakthrough of the year in 2015.[16]Bioethical concerns have been raised about the prospect of using CRISPR for germline editing.[17]

Structure of crRNA-guided E. coli Cascade complex (Cas, blue) bound to single-stranded DNA (orange).

The discovery of clustered DNA repeats began independently in three parts of the world.

The first description of what would later be called CRISPR was from Osaka University researcher Yoshizumi Ishino in 1987, who accidentally cloned part of a CRISPR together with the iap gene, the target of interest. The organization of the repeats was unusual because repeated sequences are typically arranged consecutively along DNA. The function of the interrupted clustered repeats was not known at the time.[18][19]

In 1993 researchers of Mycobacterium tuberculosis in the Netherlands published two articles about a cluster of interrupted direct repeats (DR) in this bacterium. These researchers recognized the diversity of the DR-intervening sequences among different strains of M. tuberculosis[20] and used this property to design a typing method that was named Spoligotyping, which is still in use today.[21][22]

At the same time, repeats were observed in the archaeal organisms Haloferax and Haloarcula species, and their function was studied by Francisco Mojica at the University of Alicante in Spain. Although his hypothesis turned out to be wrong, Mojica surmised at the time that the clustered repeats had a role in correctly segregating replicated DNA into daughter cells during cell division because plasmids and chromosomes with identical repeat arrays could not coexist in Haloferax volcanii. Transcription of the interrupted repeats was also noted for the first time.[22][23] By 2000, Mojica's group had identified interrupted repeats in 20 species of microbes.[24] In 2001, Mojica and Ruud Jansen, who was searching for additional interrupted repeats, proposed the acronym CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to alleviate the confusion stemming from the numerous acronyms used to describe the sequences in the scientific literature.[23][25]

A major addition to the understanding of CRISPR came with Jansen's observation that the prokaryote repeat cluster was accompanied by a set of homologous genes that make up CRISPR-associated systems or cas genes. Four cas genes (cas 1 to 4) were initially recognized. The Cas proteins showed helicase and nuclease motifs, suggesting a role in the dynamic structure of the CRISPR loci.[26] In this publication the acronym CRISPR was coined as the universal name of this pattern. However, the CRISPR function remained enigmatic.

In 2005, three independent research groups showed that some CRISPR spacers are derived from phage DNA and extrachromosomal DNA such as plasmids.[27][28][29] In effect, the spacers are fragments of DNA gathered from viruses that previously tried to attack the cell. The source of the spacers was a sign that the CRISPR/cas system could have a role in adaptive immunity in bacteria.[1][30] All three studies proposing this idea were initially rejected by high-profile journals, but eventually appeared in other journals.[31]

The first publication[28] proposing a role of CRISPR-Cas in microbial immunity, by Mojica's group, predicted a role for the RNA transcript of spacers on target recognition in a mechanism that could be analogous to the RNA interference system used by eukaryotic cells. Koonin and colleagues extended that hypothesis by proposing mechanisms of action for the different CRISPR-Cas subtypes according to the predicted function of their proteins.[32] Others hypothesized that CRISPR sequences directed Cas enzymes to degrade viral DNA.[19][29]

Experimental work by several groups revealed the basic mechanisms of CRISPR-Cas immunity. In 2007 the first experimental evidence that CRISPR was an adaptive immune system was published.[19] A CRISPR region in Streptococcus thermophilus acquired spacers from the DNA of an infecting bacteriophage. The researchers manipulated the resistance of S. thermophilus to phage by adding and deleting spacers whose sequence matched those found in the tested phages.[33][34] In 2008, Brouns and colleagues identified a complex of Cas protein that in E. coli cut the CRISPR RNA within the repeats into spacer-containing RNA molecules, which remained bound to the protein complex. That year Marraffini and Sontheimer showed that a CRISPR sequence of S. epidermidis targeted DNA and not RNA to prevent conjugation. This finding was at odds with the proposed RNA-interference-like mechanism of CRISPR-Cas immunity, although a CRISPR-Cas system that targets foreign RNA was later found in Pyrococcus furiosus.[19][33] A 2010 study showed that CRISPR-Cas cuts both strands of phage and plasmid DNA in S. thermophilus.[35]

Researchers studied a simpler CRISPR system from Streptococcus pyogenes that relies on the protein Cas9. The Cas9 endonuclease is a four-component system that includes two small RNA molecules named CRISPR RNA (crRNA) and trans-activating CRISPR RNA (tracrRNA).[36]Jennifer Doudna and Emmanuelle Charpentier re-engineered the Cas9 endonuclease into a more manageable two-component system by fusing the two RNA molecules into a "single-guide RNA" that, when mixed with Cas9, could find and cut the DNA target specified by the guide RNA. By manipulating the nucleotide sequence of the guide RNA, the artificial Cas9 system could be programmed to target any DNA sequence for cleavage.[37] Another group of collaborators comprising iknys together with Gainas, Barrangou and Horvath showed that Cas9 from the S. thermophilus CRISPR system can also be reprogrammed to target a site of their choosing by changing the sequence of its crRNA. These advances fueled efforts to edit genomes with the modified CRISPR-Cas9 system.[22]

Feng Zhang's and George Church's groups simultaneously described genome editing in human cell cultures using CRISPR-Cas9 for the first time.[19][38][39] It has since been used in a wide range of organisms, including baker's yeast (Saccharomyces cerevisiae),[40][41][42] zebrafish (D. rerio),[43] fruit flies (Drosophila melanogaster),[44] nematodes (C. elegans),[45] plants,[46] mice,[47] monkeys[48] and human embryos.[49]

CRISPR has been modified to make programmable transcription factors that allow scientists to target and activate or silence specific genes.[50]

In 2015, the nuclease Cpf1 was discovered in the CRISPR/Cpf1 system of the bacterium Francisella novicida.[51][52] Cpf1 showed several key differences from Cas9 including: causing a 'staggered' cut in double stranded DNA as opposed to the 'blunt' cut produced by Cas9, relying on a 'T rich' PAM (providing alternate targeting sites to Cas9) and requiring only a CRISPR RNA (crRNA) for successful targeting. By contrast Cas9 requires both crRNA and a transactivating crRNA (tracrRNA)).

In the early 2000s, researchers developed zinc finger nucleases, synthetic proteins whose DNA-binding domains enable them to create double-stranded breaks in DNA at specific points. In 2010, synthetic nucleases called transcription activator-like effector nucleases (TALENs) provided an easier way to target a double-stranded break to a specific location on the DNA strand. Both zinc finger nucleases and TALENs require the creation of a custom protein for each targeted DNA sequence, which is a more difficult and time-consuming process than that for guide RNAs. CRISPRs are much easier to design because the process requires making only a short RNA sequence.[53]

The CRISPR array comprises an AT-rich leader sequence followed by short repeats that are separated by unique spacers.[54] CRISPR repeats typically range in size from 28 to 37 base pairs (bps), though there can be as few as 23 bp and as many as 55 bp.[55] Some show dyad symmetry, implying the formation of a secondary structure such as a hairpin in the RNA, while others are predicted to be unstructured. The size of spacers in different CRISPR arrays is typically 32 to 38 bp (range 21 to 72 bp).[55] New spacers can appear rapidly as part of the immune response to phage infection.[56] There are usually fewer than 50 units of the repeat-spacer sequence in a CRISPR array.[55]

Small clusters of cas genes are often located next to CRISPR repeat-spacer arrays. Collectively there are 93 cas genes that are grouped into 35 families based on sequence similarity of the encoded proteins. 11 of the 35 families form the cas core, which includes the protein families Cas1 through Cas9. A complete CRISPR-Cas locus has at least one gene belonging to the cas core.[57]

CRISPR-Cas systems fall into two classes. Class 1 systems use a complex of multiple Cas proteins to degrade foreign nucleic acids. Class 2 systems use a single large Cas protein for the same purpose. Class 1 is divided into types I, III, and IV; class 2 is divided into types II, V, and VI.[58] The 6 system types are divided into 19 subtypes.[59] Each type and most subtypes are characterized by a "signature gene" found almost exclusively in the category. Classification is also based on the complement of cas genes that are present. Most CRISPR-Cas systems have a Cas1 protein. The phylogeny of Cas1 proteins generally agrees with the classification system.[57] Many organisms contain multiple CRISPR-Cas systems suggesting that they are compatible and may share components.[60][61] The sporadic distribution of the CRISPR/Cas subtypes suggests that the CRISPR/Cas system is subject to horizontal gene transfer during microbial evolution.

CRISPR-Cas immunity is a natural process of bacteria and archaea. CRISPR-Cas prevents bacteriophage infection, conjugation and natural transformation by degrading foreign nucleic acids that enter the cell.[33]

When a microbe is invaded by a virus, the first stage of the immune response is to capture viral DNA and insert it into a CRISPR locus in the form of a spacer. Cas1 and Cas2 are found in all three types of CRISPR-Cas immune systems, which indicates that they are involved in spacer acquisition. Mutation studies confirmed this hypothesis, showing that removal of cas1 or cas2 stopped spacer acquisition, without affecting CRISPR immune response.[70][71][72][73][74]

Multiple Cas1 proteins have been characterised and their structures resolved.[75][76][77] Cas1 proteins have diverse amino acid sequences. However, their crystal structures are similar and all purified Cas1 proteins are metal-dependent nucleases/integrases that bind to DNA in a sequence-independent manner.[60] Representative Cas2 proteins have been characterised and possess either (single strand) ssRNA-[78] or (double strand) dsDNA-[79][80] specific endoribonuclease activity.

In the I-E system of E. coli Cas1 and Cas2 form a complex where a Cas2 dimer bridges two Cas1 dimers.[81] In this complex Cas2 performs a non-enzymatic scaffolding role,[81] binding double-stranded fragments of invading DNA, while Cas1 binds the single-stranded flanks of the DNA and catalyses their integration into CRISPR arrays.[82][83][84]

Bioinformatic analysis of regions of phage genomes that were excised as spacers (termed protospacers) revealed that they were not randomly selected but instead were found adjacent to short (3 5 bp) DNA sequences termed protospacer adjacent motifs (PAM). Analysis of CRISPR-Cas systems showed PAMs to be important for type I and type II, but not type III systems during acquisition.[29][85][86][87][88][89] In type I and type II systems, protospacers are excised at positions adjacent to a PAM sequence, with the other end of the spacer cut using a ruler mechanism, thus maintaining the regularity of the spacer size in the CRISPR array.[90][91] The conservation of the PAM sequence differs between CRISPR-Cas systems and appears to be evolutionarily linked to Cas1 and the leader sequence.[89][92]

New spacers are added to a CRISPR array in a directional manner,[27] occurring preferentially,[56][85][86][93][94] but not exclusively, adjacent[88][91] to the leader sequence. Analysis of the type I-E system from E. coli demonstrated that the first direct repeat adjacent to the leader sequence, is copied, with the newly acquired spacer inserted between the first and second direct repeats.[73][90]

The PAM sequence appears to be important during spacer insertion in type I-E systems. That sequence contains a strongly conserved final nucleotide (nt) adjacent to the first nt of the protospacer. This nt becomes the final base in the first direct repeat.[74][95][96] This suggests that the spacer acquisition machinery generates single-stranded overhangs in the second-to-last position of the direct repeat and in the PAM during spacer insertion. However, not all CRISPR-Cas systems appear to share this mechanism as PAMs in other organisms do not show the same level of conservation in the final position.[92] It is likely that in those systems, a blunt end is generated at the very end of the direct repeat and the protospacer during acquisition.

Analysis of Sulfolobus solfataricus CRISPRs revealed further complexities to the canonical model of spacer insertion, as one of its six CRISPR loci inserted new spacers randomly throughout its CRISPR array, as opposed to inserting closest to the leader sequence.[91]

Multiple CRISPRs contain many spacers to the same phage. The mechanism that causes this phenomenon was discovered in the type I-E system of E. coli. A significant enhancement in spacer acquisition was detected where spacers already target the phage, even mismatches to the protospacer. This priming requires the Cas proteins involved in both acquisition and interference to interact with each other. Newly acquired spacers that result from the priming mechanism are always found on the same strand as the priming spacer.[74][95][96] This observation led to the hypothesis that the acquisition machinery slides along the foreign DNA after priming to find a new protospacer.[96]

CRISPR-RNA (crRNA), which later guides the Cas nuclease to the target during the interference step, must be generated from the CRISPR sequence. The crRNA is initially transcribed as part of a single long transcript encompassing much of the CRISPR array.[5] This transcript is then cleaved by Cas proteins to form crRNAs. The mechanism to produce crRNAs differs among CRISPR-Cas systems. In type I-E and type I-F systems, the proteins Cas6e and Cas6f respectively, recognise stem-loops[97][98][99] created by the pairing of identical repeats that flank the crRNA.[100] These Cas proteins cleave the longer transcript at the edge of the paired region, leaving a single crRNA along with a small remnant of the paired repeat region.

Type III systems also use Cas6, however their repeats do not produce stem-loops. Cleavage instead occurs by the longer transcript wrapping around the Cas6 to allow cleavage just upstream of the repeat sequence.[101][102][103]

Type II systems lack the Cas6 gene and instead utilize RNaseIII for cleavage. Functional type II systems encode an extra small RNA that is complementary to the repeat sequence, known as a trans-activating crRNA (tracrRNA).[71] Transcription of the tracrRNA and the primary CRISPR transcript results in base pairing and the formation of dsRNA at the repeat sequence, which is subsequently targeted by RNaseIII to produce crRNAs. Unlike the other two systems the crRNA does not contain the full spacer, which is instead truncated at one end.[66]

CrRNAs associate with Cas proteins to form ribonucleotide complexes that recognize foreign nucleic acids. CrRNAs show no preference between the coding and non-coding strands, which is indicative of an RNA-guided DNA-targeting system.[8][35][70][74][104][105][106] The type I-E complex (commonly referred to as Cascade) requires five Cas proteins bound to a single crRNA.[107][108]

During the interference stage in type I systems the PAM sequence is recognized on the crRNA-complementary strand and is required along with crRNA annealing. In type I systems correct base pairing between the crRNA and the protospacer signals a conformational change in Cascade that recruits Cas3 for DNA degradation.

Type II systems rely on a single multifunctional protein, Cas9, for the interference step.[66]Cas9 requires both the crRNA and the tracrRNA to function and cleaves DNA using its dual HNH and RuvC/RNaseH-like endonuclease domains. Basepairing between the PAM and the phage genome is required in type II systems. However, the PAM is recognized on the same strand as the crRNA (the opposite strand to type I systems).

Type III systems, like type I require six or seven Cas proteins binding to crRNAs.[109][110] The type III systems analysed from S. solfataricus and P. furiosus both target the mRNA of phages rather than phage DNA genome,[61][110] which may make these systems uniquely capable of targeting RNA-based phage genomes.[60]

The mechanism for distinguishing self from foreign DNA during interference is built into the crRNAs and is therefore likely common to all three systems. Throughout the distinctive maturation process of each major type, all crRNAs contain a spacer sequence and some portion of the repeat at one or both ends. It is the partial repeat sequence that prevents the CRISPR-Cas system from targeting the chromosome as base pairing beyond the spacer sequence signals self and prevents DNA cleavage.[111] RNA-guided CRISPR enzymes are classified as type V restriction enzymes.

A bioinformatic study showed that CRISPRs are evolutionarily conserved and cluster into related types. Many show signs of a conserved secondary structure.[100]

CRISPR/Cas can immunize bacteria against certain phages and thus halt transmission. For this reason, Koonin described CRISPR/Cas as a Lamarckian inheritance mechanism.[112] However, this was disputed by a critic who noted, "We should remember [Lamarck] for the good he contributed to science, not for things that resemble his theory only superficially. Indeed, thinking of CRISPR and other phenomena as Lamarckian only obscures the simple and elegant way evolution really works".[113]

Analysis of CRISPR sequences revealed coevolution of host and viral genomes.[114] Cas9 proteins are highly enriched in pathogenic and commensal bacteria. CRISPR/Cas-mediated gene regulation may contribute to the regulation of endogenous bacterial genes, particularly during interaction with eukaryotic hosts. For example, Francisella novicida uses a unique, small, CRISPR/Cas-associated RNA (scaRNA) to repress an endogenous transcript encoding a bacterial lipoprotein that is critical for F. novicida to dampen host response and promote virulence.[115]

The basic model of CRISPR evolution is newly incorporated spacers driving phages to mutate their genomes to avoid the bacterial immune response, creating diversity in both the phage and host populations. To fight off a phage infection, the sequence of the CRISPR spacer must correspond perfectly to the sequence of the target phage gene. Phages can continue to infect their hosts given point mutations in the spacer.[111] Similar stringency is required in PAM or the bacterial strain remains phage sensitive.[86][111]

A study of 124 S. thermophilus strains showed that 26% of all spacers were unique and that different CRISPR loci showed different rates of spacer acquisition.[85] Some CRISPR loci evolve more rapidly than others, which allowed the strains' phylogenetic relationships to be determined. A comparative genomic analysis showed that E. coli and S. enterica evolve much more slowly than S. thermophilus. The latter's strains that diverged 250 thousand years ago still contained the same spacer complement.[116]

Metagenomic analysis of two acid mine drainage biofilms showed that one of the analyzed CRISPRs contained extensive deletions and spacer additions versus the other biofilm, suggesting a higher phage activity/prevalence in one community than the other.[56] In the oral cavity, a temporal study determined that 7-22% of spacers were shared over 17 months within an individual while less than 2% were shared across individuals.[94]

From the same environment a single strain was tracked using PCR primers specific to its CRISPR system. Broad-level results of spacer presence/absence showed significant diversity. However, this CRISPR added 3 spacers over 17 months,[94] suggesting that even in an environment with significant CRISPR diversity some loci evolve slowly.

CRISPRs were analysed from the metagenomes produced for the human microbiome project.[117] Although most were body-site specific, some within a body site are widely shared among individuals. One of these loci originated from streptococcal species and contained ~15,000 spacers, 50% of which were unique. Similar to the targeted studies of the oral cavity, some showed little evolution over time.[117]

CRISPR evolution was studied in chemostats using S. thermophilus to directly examine spacer acquisition rates. In one week, S. thermophilus strains acquired up to three spacers when challenged with a single phage.[118] During the same interval the phage developed single nucleotide polymorphisms that became fixed in the population, suggesting that targeting had prevented phage replication absent these mutations.[118]

Another S. thermophilus experiment showed that phages can infect and replicate in hosts that have only one targeting spacer. Yet another showed that sensitive hosts can exist in environments with high phage titres.[119] The chemostat and observational studies suggest many nuances to CRISPR and phage (co)evolution.

CRISPRs are widely distributed among bacteria and archaea[64] and show some sequence similarities.[100] Their most notable characteristic is their repeating spacers and direct repeats. This characteristic makes CRISPRs easily identifiable in long sequences of DNA, since the number of repeats decreases the likelihood of a false positive match. Three programs used for CRISPR repeat identification search for regularly interspaced repeats in long sequences: CRT,[120] PILER-CR[121] and CRISPRfinder.[122]

Analysis of CRISPRs in metagenomic data is more challenging, as CRISPR loci do not typically assemble, due to their repetitive nature or through strain variation, which confuses assembly algorithms. Where many reference genomes are available, polymerase chain reaction (PCR) can be used to amplify CRISPR arrays and analyse spacer content.[85][94][123][124][125] However, this approach yields information only for specifically targeted CRISPRs and for organisms with sufficient representation in public databases to design reliable polymerase chain reaction (PCR) primers.

The alternative is to extract and reconstruct CRISPR arrays from shotgun metagenomic data. This is computationally more difficult, particularly with second generation sequencing technologies (e.g. 454, Illumina), as the short read lengths prevent more than two or three repeat units appearing in a single read. CRISPR identification in raw reads has been achieved using purely de novo identification[126] or by using direct repeat sequences in partially assembled CRISPR arrays from contigs (overlapping DNA segments that together represent a consensus region of DNA)[117] and direct repeat sequences from published genomes[127] as a hook for identifying direct repeats in individual reads.

Another way for bacteria to defend against phage infection is by having chromosomal islands. A subtype of chromosomal islands called phage-inducible chromosomal island (PICI) is excised from a bacterial chromosome upon phage infection and can inhibit phage replication.[128] The mechanisms that induce PICI excision and how PICI inhibits phage replication are not well understood. One study showed that lytic ICP1 phage, which specifically targets Vibrio cholerae serogroup O1, has acquired a CRISPR/Cas system that targets a V. cholera PICI-like element. The system has 2 CRISPR loci and 9 Cas genes. It seems to be homologous to the 1-F system found in Yersinia pestis. Moreover, like the bacterial CRISPR/Cas system, ICP1 CRISPR/Cas can acquire new sequences, which allows phage and host to co-evolve.[129]

By the end of 2014 some 600 research papers had been published that mentioned CRISPR.[130] The technology had been used to functionally inactivate genes in human cell lines and cells, to study Candida albicans, to modify yeasts used to make biofuels and to genetically modify crop strains.[130] CRISPR can also be used to change mosquitos so they cannot transmit diseases such as malaria.[131]

CRISPR-based re-evaluations of claims for gene-disease relationships have led to the discovery of potentially important anomalies[132]

CRISPR/Cas9 genome editing is carried out with a Type II CRISPR system. When utilized for genome editing, this system includes Cas9, crRNA, tracrRNA along with an optional section of DNA repair template that is utilized in either Non-Homologous End Joining (NHEJ) or Homology Directed Repair (HDR).

CRISPR/Cas9 often employs a plasmid to transfect the target cells.[135] The main components of this plasmid are displayed in the image and listed in the table. The crRNA needs to be designed for each application as this is the sequence that Cas9 uses to identify and directly bind to the cell's DNA. The crRNA must bind only where editing is desired. The repair template is designed for each application, as it must overlap with the sequences on either side of the cut and code for the insertion sequence.

Multiple crRNAs and the tracrRNA can be packaged together to form a single-guide RNA (sgRNA).[136] This sgRNA can be joined together with the Cas9 gene and made into a plasmid in order to be transfected into cells.

CRISPR/Cas9 offers a high degree of fidelity and relatively simple construction. It depends on two factors for its specificity: the target sequence and the PAM. The target sequence is 20 bases long as part of each CRISPR locus in the crRNA array.[135] A typical crRNA array has multiple unique target sequences. Cas9 proteins select the correct location on the host's genome by utilizing the sequence to bond with base pairs on the host DNA. The sequence is not part of the Cas9 protein and as a result is customizable and can be independently synthesized.[137][138]

The PAM sequence on the host genome is recognized by Cas9. Cas9 cannot be easily modified to recognize a different PAM sequence. However this is not too limiting as it is a short sequence and nonspecific (e.g. the SpCas9 PAM sequence is 5'-NGG-3' and in the human genome occurs roughly every 8 to 12 base pairs).[135]

Once these have been assembled into a plasmid and transfected into cells the Cas9 protein with the help of the crRNA finds the correct sequence in the host cell's DNA and depending on the Cas9 variant creates a single or double strand break in the DNA.[139]

Properly spaced single strand breaks in the host DNA can trigger homology directed repair, which is less error prone than the non-homologous end joining that typically follows a double strand break. Providing a DNA repair template allows for the insertion of a specific DNA sequence at an exact location within the genome. The repair template should extend 40 to 90 base pairs beyond the Cas9 induced DNA break.[135] The goal is for the cell's HDR process to utilize the provided repair template and thereby incorporate the new sequence into the genome. Once incorporated, this new sequence is now part of the cell's genetic material and passes into its daughter cells.

Many online tools are available to aid in designing effective sgRNA sequences.[140]

Scientists can use viral or non-viral systems for delivery of the Cas9 and sgRNA into target cells. Electroporation of DNA, RNA or ribonucleocomplexes is the most common and cheapest system. This technique was used to edit CXCR4 and PD-1, knocking in new sequences to replace specific genetic "letters" in these proteins. The group was then able to sort the cells, using cell surface markers, to help identify successfully edited cells.[141] Deep sequencing of a target site confirmed that knock-in genome modifications had occurred with up to 20% efficiency, which accounted for up to approximately one-third of total editing events.[142] However, hard-to-transfect cells (stem cells, neurons, hematopoietic cells, etc.) require more efficient delivery systems such as those based on lentivirus (LVs), adenovirus (AdV) and adeno-associated virus (AAV).

CRISPRs have been used to cut five[34] to 62 genes at once: pig cells have been engineered to inactivate all 62 Porcine Endogenous Retroviruses in the pig genome, which eliminated transinfection from the pig to human cells in culture.[143] CRISPR's low cost compared to alternatives is widely seen as revolutionary.[11][12]

Selective engineered redirection of the CRISPR/Cas system was first demonstrated in 2012 in:[144][145]

Several variants of CRISPR/Cas9 allow gene activation or genome editing with an external trigger such as light or small molecules.[148][149][150] These include photoactivatable CRISPR systems developed by fusing light-responsive protein partners with an activator domain and a dCas9 for gene activation,[151][152] or fusing similar light responsive domains with two constructs of split-Cas9,[153][154] or by incorporating caged unnatural amino acids into Cas9,[155] or by modifying the guide RNAs with photocleavable complements for genome editing.[156]

Methods to control genome editing with small molecules include an allosteric Cas9, with no detectable background editing, that will activate binding and cleavage upon the addition of 4-hydroxytamoxifen (4-HT),[148] 4-HT responsive intein-linked Cas9s[157] or a Cas9 that is 4-HT responsive when fused to four ERT2 domains.[158] Intein-inducible split-Cas9 allows dimerization of Cas9 fragments[159] and Rapamycin-inducible split-Cas9 system developed by fusing two constructs of split Cas9 with FRB and FKBP fragments.[160] Furthermore, other studies have shown to induce transcription of Cas9 with a small molecule, doxycyline.[161][162] Small molecules can also be used to improve Homology Directed Repair (HDR),[163] often by inhibiting the Non-Homologous End Joining (NHEJ) pathway.[164] These systems allow conditional control of CRISPR activity for improved precision, efficiency and spatiotemporal control.

Using "dead" versions of Cas9 (dCas9) eliminates CRISPR's DNA-cutting ability, while preserving its ability to target desirable sequences. Multiple groups added various regulatory factors to dCas9s, enabling them to turn almost any gene on or off or adjust its level of activity.[165] Like RNAi, CRISPR interference (CRISPRi) turns off genes in a reversible fashion by targeting, but not cutting a site. The targeted site is methylated, epigenetically modifying the gene. This modification inhibits transcription. Cas9 is an effective way of targeting and silencing specific genes at the DNA level.[166] In bacteria, the presence of Cas9 alone is enough to block transcription. For mammalian applications, a section of protein is added. Its guide RNA targets regulatory DNA sequences called promoters that immediately precede the target gene.[34]

Cas9 was used to carry synthetic transcription factors that activated specific human genes. The technique achieved a strong effect by targeting multiple CRISPR constructs to slightly different locations on the gene's promoter.[34]

In 2016 researchers demonstrated that CRISPR from an ordinary mouth bacterium could be used to edit RNA. The researchers searched databases containing hundreds of millions of genetic sequences for those that resembled Crispr genes. They considered the fusobacteria Leptotrichia shahii. It had a group of genes that resembled CRISPR genes, but with important differences. When the researchers equipped other bacteria with these genes, which they called C2c2, they found that the organisms gained a novel defense.[167]

Many viruses encode their genetic information in RNA rather than DNA that they repurpose to make new viruses. HIV and poliovirus are such viruses. Bacteria with C2c2 make molecules that can dismember RNA, destroying the virus. Tailoring these genes opened any RNA molecule to editing.[167]

CRISPR simplifies creation of animals for research that mimic disease or show what happens when a gene is knocked down or mutated. CRISPR may be used at the germline level to create animals where the gene is changed everywhere, or it may be targeted at non-germline cells.[168][169][170]

CRISPR can be utilized to create human cellular models of disease. For instance, applied to human pluripotent stem cells CRISPR introduced targeted mutations in genes relevant to polycystic kidney disease (PKD) and focal segmental glomerulosclerosis (FSG).[171] These CRISPR-modified pluripotent stem cells were subsequently grown into human kidney organoids that exhibited disease-specific phenotypes. Kidney organoids from stem cells with PKD populations formed large, translucent cyst structures from kidney tubules. Kidney organoids with mutations in a gene linked to FSG developed junctional defects between podocytes, the filtering cells affected in that disease. Importantly, these disease phenotypes were absent in control organoids of identical genetic background, but lacking the CRISPR modifications.[171]

A similar approach was taken to model long QT syndrome in cardiomyocytes derived from pluripotent stem cells.[172] These CRISPR-generated cellular models, with isogenic controls, provide a new way to study human disease and test drugs.

In 2003 evolutionary biologist Austin Burt envisioned attaching a gene that coded for a desired trait to "selfish" DNA elements that could copy themselves from one chromosome position to another. That would bias daughter cells to inherit it, quickly spreading it throughout a population. In 2015 a U.S. team used CRISPR to create a "mutagenic chain reaction" that drove a pigmentation trait in lab-grown Drosophila to the next generation with 97% efficiency. With another research group they created a gene drive in mosquitoes that spread genes that prevented the insects from harboring malaria parasites. Weeks later, the team reported a second drive with genes that rendered female mosquitoes infertile and could quickly wipe out a population.[165]

CRISPR/Cas-based "RNA-guided nucleases" can be used to target virulence factors, genes encoding antibiotic resistance and other medically relevant sequences of interest. This technology thus represents a novel form of antimicrobial therapy and a strategy by which to manipulate bacterial populations.[173][174] Some of the affected genes are tied to human diseases, including those involved in muscle differentiation, cancer, inflammation and fetal hemoglobin.[34]

Research suggests that CRISPR is an effective way to limit replication of multiple herpesviruses. It was able to eradicate viral DNA in the case of Epstein-Barr virus (EBV). Anti-herpesvirus CRISPRs have promising applications such as removing cancer-causing EBV from tumor cells, helping rid donated organs for immunocompromised patients of viral invaders, or preventing cold sore outbreaks and recurrent eye infections by blocking HSV-1 reactivation. As of August 2016, these were awaiting testing.[175] CRISPR is being appied to develop tissue-based treatments for cancer and other diseases.[165][176]

CRISPR may revive the concept of transplanting animal organs into people. Retroviruses present in animal genomes could harm transplant recipients. In 2015 a team eliminated 62 copies of a retrovirus's DNA from the pig genome.[165]

CRISPR may have applications in tissue engineering and regenerative medicine, such as by creating human blood vessels that lack expression of MHC class II proteins, which often cause transplant rejection.[177]

In 2015, multiple studies attempted to systematically disable each individual human gene, in an attempt to identify which genes were essential to human biology. Between 1,600 and 1,800 genes passed this testof the 20,000 or so known human genes. Such genes are more strongly activated, and unlikely to carry disabling mutations. They are more likely to have indispensable counterparts in other species. They build proteins that unite to form larger collaborative complexes. The studies also catalogued the essential genes in four cancer-cell lines and identified genes that are expendable in healthy cells, but crucial in specific tumor types and drugs that could target these rogue genes.[178]

The specific functions of some 18 percent of the essential genes are unidentified. In one 2015 targeting experiment, disabling individual genes in groups of cells attempted to identify those involved in resistance to a melanoma drug. Each such gene manipulation is itself a separate "drug", potentially opening the entire genome to CRISPR-based regulation.[165]

Unenriched sequencing libraries often have abundant undesired sequences. Cas9 can specifically deplete the undesired sequences with double strand breakage with up to 99% efficiency and without significant off-target effects as seen with restriction enzymes. Treatment with Cas9 can deplete abundant rRNA while increasing pathogen sensitivity in RNA-seq libraries.[179]

As of December 2014, patent rights to CRISPR were contested. Several companies formed to develop related drugs and research tools.[180] As companies ramp up financing, doubts as to whether CRISPR can be quickly monetized were raised.[181] In February 2017 the US patent office ruled on a patent interference case brought by University of California with respect to patents issued to the Broad Institute, and found that the Broad patents, with claims covering the application of CRISPR/cas9 in eukaryotic cells, were distinct from the inventions claimed by University of California.[182][183][184]

As of November 2013, SAGE Labs (now part of Horizon Discovery group) had exclusive rights from one of those companies to produce and sell genetically engineered rats and non-exclusive rights for mouse and rabbit models.[185] By 2015[update], Thermo Fisher Scientific had licensed intellectual property from ToolGen to develop CRISPR reagent kits.[186]

At least four labs in the US, labs in China and the UK, and a US biotechnology company called Ovascience announced plans or ongoing research to apply CRISPR to human embryos.[187] Scientists, including a CRISPR co-inventor, urged a worldwide moratorium on applying CRISPR to the human germline, especially for clinical use. They said "scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans" until the full implications "are discussed among scientific and governmental organizations".[49][188] These scientists support basic research on CRISPR and do not see CRISPR as developed enough for any clinical use in making heritable changes to humans.[189]

In April 2015, Chinese scientists reported results of an attempt to alter the DNA of non-viable human embryos using CRISPR to correct a mutation that causes beta thalassemia, a lethal heritable disorder.[190][191] The study had previously been rejected by both Nature and Science in part because of ethical concerns.[192] The experiments resulted in changing only some genes, and had off-target effects on other genes. The researchers stated that CRISPR is not ready for clinical application in reproductive medicine.[192] In April 2016 Chinese scientists were reported to have made a second unsuccessful attempt to alter the DNA of non-viable human embryos using CRISPR - this time to alter the CCR5 gene to make the embryo HIV resistant.[193]

In December 2015, an International Summit on Human Gene Editing took place in Washington under the guidance of David Baltimore. Members of national scientific academies of America, Britain and China discussed the ethics of germline modification. They agreed to support basic and clinical research under appropriate legal and ethical guidelines. A specific distinction was made between somatic cells, where the effects of edits are limited to a single individual, versus germline cells, where genome changes could be inherited by future generations. Heritable modifications could have unintended and far-reaching consequences for human evolution, genetically (e.g. gene/environment interactions) and culturally (e.g. Social Darwinism). Altering of gametocytes and embryos to generate inheritable changes in humans was defined to be irresponsible. The group agreed to initiate an international forum to address such concerns and harmonize regulations across countries.[194]

Policy regulations for the CRISPR/cas9 system vary around the globe. In February 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR-Cas9 and related techniques. However, researchers were forbidden from implanting the embryos and the embryos were to be destroyed after seven days.[195]

The US has an elaborate, interdepartmental regulatory system to evaluate new genetically modified foods and crops. For example, the Agriculture Risk Protection Act of 2000 gives the USDA the authority to oversee the detection, control, eradication, suppression, prevention, or retardation of the spread of plant pests or noxious weeds to protect the agriculture, environment and economy of the US. The act regulates any genetically modified organism that utilizes the genome of a predefined 'plant pest' or any plant not previously categorized.[196] In 2015, Yang successfully deactivated 16 specific genes in the white button mushroom. Since he had not added any foreign DNA to his organism, the mushroom could not be regulated under by the USDA under Section 340.2.[197] Yang's white button mushroom was the first organism genetically modified with the Crispr/cas9 protein system to pass US regulation.[198] In 2016, the USDA sponsored a committee to consider future regulatory policy for upcoming genetic modification techniques. With the help of the US National Academies of Sciences, Engineering and Medicine, special interests groups met on April 15 to contemplate the possible advancements in genetic engineering within the next 5 years and potential policy regulations that would need to come into play.[199] With the emergence of rogue genetic engineers employing the technology, the FDA has begun issuing new regulations.[200]

In 2012 and 2013, CRISPR was a runner-up in Science Magazine's Breakthrough of the Year award. In 2015, it was the winner of that award.[165] CRISPR was named as one of MIT Technology Review's 10 breakthroughs technologies in 2014 and 2016.[201][202]

CRISPR-DR2: Secondary structure taken from the Rfam database. Family RF01315.

CRISPR-DR5: Secondary structure taken from the Rfam database. Family RF011318.

CRISPR-DR6: Secondary structure taken from the Rfam database. Family RF01319.

CRISPR-DR8: Secondary structure taken from the Rfam database. Family RF01321.

CRISPR-DR9: Secondary structure taken from the Rfam database. Family RF01322.

CRISPR-DR19: Secondary structure taken from the Rfam database. Family RF01332.

CRISPR-DR41: Secondary structure taken from the Rfam database. Family RF01350.

CRISPR-DR52: Secondary structure taken from the Rfam database. Family RF01365.

CRISPR-DR57: Secondary structure taken from the Rfam database. Family RF01370.

CRISPR-DR65: Secondary structure taken from the Rfam database. Family RF01378.

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