Category Archives: Gene Medicine

National Institutes of Health (press release)

NIAID scientists discover rare genetic susceptibility to common cold National Institutes of Health (press release) The case, published online today in the Journal of Experimental Medicine, reveals an important mechanism by which the immune system responds to these viruses, say the study authors. Several weeks after birth, the child began experiencing life ... and more »

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NIAID scientists discover rare genetic susceptibility to common cold - National Institutes of Health (press release)

The artificial intelligence that can blow human pilots out of the sky in air-to-air combat accurately predicted treatment outcomes for bipolar disorder, according to a new medical study by the University of Cincinnati. The findings open a world of possibility for using AI, or machine learning, to treat disease, researchers said. David Fleck, an associate professor at the UC College of Medicine, and his co-authors used artificial intelligence called genetic fuzzy trees to predict how bipolar patients would respond to lithium. Bipolar disorder, depicted in the TV show Homeland and the Oscar-winning Silver Linings Playbook, affects as many as 6 million adults in the United States or four percent of the adult population in a given year. In psychiatry, treatment of bipolar disorder is as much an art as a science, Fleck said. Patients are fluctuating between periods of mania and depression. Treatments will change during those periods. Its really difficult to treat them appropriately during stages of the illness.

The study authors found that even the best of eight common models used in treating bipolar disorder predicted who would respond to lithium treatment with 75 percent accuracy. By comparison, the model UC researchers developed using AI predicted how patients would respond to lithium 100 percent of the time. Even more impressively, the UC model predicted the actual reduction in manic symptoms after lithium treatment with 92 percent accuracy. The study authors found that even the best of the eight most common treatments was only effective half the time. But the model UC researchers developed using AI predicted how patients would respond to lithium treatment with 88 percent accuracy and 80 percent accuracy in validation. It turns out that the same kind of artificial intelligence that outmaneuvered Air Force pilots last year in simulation after simulation at Wright-Patterson Air Force Base is equally adept at making beneficial decisions that can help doctors treat disease. The findings were published this month in the journal Bipolar Disorders. What this shows is that an effort funded for aerospace is a game-changer for the field of medicine. And that is awesome, said Kelly Cohen, a professor in UCs College of Engineering and Applied Science. Cohens doctoral graduate Nicholas Ernest is founder of the company Psibernetix, Inc., an artificial intelligence development and consultation company. Psibernetix is working on applications such as air-to-air combat, cybersecurity and predictive analytics. Ernests fuzzy logic algorithm is able to sort vast possibilities to arrive at the best choices in literally the blink of an eye. Normally the problems our AIs solve have many, many googolplexes of possible solutions effectively infinite, study co-author Ernest said.

His team developed a genetic fuzzy logic called Alpha capable of shooting down human pilots in simulations, even when the computers aircraft intentionally was handicapped with a slower top speed and less nimble flight characteristics. The systems autonomous real-time decision-making shot down retired U.S. Air Force Col. Gene Lee in every engagement. It seemed to be aware of my intentions and reacting instantly to my changes in flight and my missile deployment, Lee said last year. It knew how to defeat the shot I was taking. It moved instantly between defensive and offensive actions as needed.

The American Institute of Aeronautics and Astronautics honored Cohen and Ernest this year for their advancement and application of artificial intelligence to large scale, meaningful and challenging aerospace-related problems. Cohen spent much of his career working with fuzzy-logic based AI in drones. He used a sabbatical from the engineering college to approach the UC College of Medicine with an idea: What if they could apply the amazing predictive power of fuzzy logic to a particularly nettlesome medical problem? Medicine and avionics have little in common. But each entails an ordered process a vast decision tree to arrive at the best choices. Fuzzy logic is a system that relies not on specific definitions but generalizations to compensate for uncertainty or statistical noise. This artificial intelligence is called genetic fuzzy because it constantly refines its answer, tossing out the lesser choices in a way analogous to the genetic processes of Darwinian natural selection. Cohen compares it to teaching a child how to recognize a chair. After seeing just a few examples, any child can identify the object people sit in as a chair, regardless of its shape, size or color. We do not require a large statistical database to learn. We figure things out. We do something similar to emulate that with fuzzy logic, Cohen said.

Cohen found a receptive audience in Fleck, who was working with UCs former Center for Imaging Research. After all, who better to tackle one of medical sciences hardest problems than a rocket scientist? Cohen, an aerospace engineer, felt up to the task. Ernest said people should not conflate the technology with its applications. The algorithm he developed is not a sentient being like the villains in the Terminator movie franchise but merely a tool, he said, albeit a powerful one with seemingly endless applications. I get emails and comments every week from would-be John Connors out there who think this will lead to the end of the world, Ernest said. Ernests company created EVE, a genetic fuzzy AI that specializes in the creation of other genetic fuzzy AIs. EVE came up with a predictive model for patient data called the LITHium Intelligent Agent or LITHIA for the bipolar study. This predictive model taps into the power of fuzzy logic to allow you to make a more informed decision, Ernest said. And unlike other types of AI, fuzzy logic can describe in simple language why it made its choices, he said. The researchers teamed up with Dr. Caleb Adler, the UC Department of Psychiatry and Behavioral Neuroscience vice chairman of clinical research, to examine bipolar disorder, a common, recurrent and often lifelong illness. Despite the prevalence of mood disorders, their causes are poorly understood, Adler said. Really, its a black box, Adler said. We diagnose someone with bipolar disorder. Thats a description of their symptoms. But that doesnt mean everyone has the same underlying causes. Selecting the appropriate treatment can be equally tricky. Over the past 15 years there has been an explosion of treatments for mania. We have more options. But we dont know who is going to respond to what, Adler said. If we could predict who would respond better to treatment, you would save time and consequences. With appropriate care, bipolar disorder is a manageable chronic illness for patients whose lives can return to normal, he said.

UCs new study, funded in part by a grant from the National Institute of Mental Health, identified 20 patients who were prescribed lithium for eight weeks to treat a manic episode. Fifteen of the 20 patients responded well to the treatment. The algorithm used an analysis of two types of patient brain scans, among other data, to predict with 100 percent accuracy which patients responded well and which didnt. And the algorithm also predicted the reductions in symptoms at eight weeks, an achievement made even more impressive by the fact that only objective biological data were used for prediction rather than subjective opinions from experienced physicians. This is a huge first step and ultimately something that will be very important to psychiatry and across medicine, Adler said. How much potential does this have to revolutionize medicine? I think its unlimited, Fleck said. Its a good result. The best way to validate it is to get a new cohort of individuals and apply their data to the system. Cohen is less reserved in his enthusiasm. He said the model could help personalize medicine to individual patients like never before, making health care both safer and more affordable. Fewer side-effects means fewer hospital visits, less secondary medication and better treatments. Now the UC researchers and Psibernetix are working on a new study applying fuzzy logic to diagnosing and treating concussions, another condition that has bedeviled doctors. The impact on society could be profound, Cohen said.

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AI that Can Shoot Down Fighter Planes Helps Treat Bipolar Disorder - Laboratory Equipment

A man showing early signs of a heart attack detected by a bot tracking his heart activity from a sensor on his wrist is picked up by a self-driving car that checks his vital signs on the way to the hospital. There, his doctors video-conference with a specialist, who assesses his symptoms through a Skype-like screen and recommends a treatment plan.

The scenario, inconceivable a generation ago, is closer than you might think. Technological advancements are ushering in a new era of health care, eroding the long-held model of hospitals and doctors offices as the physical center of the health system. The change is unfolding on many fronts, and experts say we are on the cusp of a revolution that could come within the next decade.

The growth of telemedicine (video chats with your doctor) and tools to track chronic diseases (wearable glucose-monitoring devices for diabetics) is inching us toward a time when medical care and diagnoses can be accessed from afar, and often without having to see a physician in person.

The explosion of relatively inexpensive direct-to-consumer genetic tests is allowing millions of people to learn potentially life-changing medical information about themselves without ever stepping foot in a doctors office.

And cutting-edge research in gene therapy is opening the door to the possibility of people with genetic diseases being treated much earlier in life, and being cured for longer periods of time potentially improving the quality of life for millions.

This rapidly changing landscape raises the question: Will there come a day when we wont need to go to the doctors office anymore? Will we be able to navigate the health system without coming into contact with a medical professional? And would that be good or bad?

Unit coordinator Ricky Ng does prep work for recently admitted patients and supports patient information for critical care nurses at California Pacific Medical Center's eICU hub.

Unit coordinator Ricky Ng does prep work for recently admitted...

Developers of self-driving cars are already considering including some basic inward-facing sensors that can be used for medical applications such as those that can measure temperature or cameras that can visually assess the health of a passenger to aid the elderly and people with disabilities, according to Nidhi Kalra, senior information scientist at the think tank Rand Corp. who researches autonomous car policy.

Unit coordinator Ricky Ng (left) talks with critical care nurse Clark Wurth at California Pacific Medical Centers eICU hub, where off-site ICU patients are monitored on computers.

Unit coordinator Ricky Ng (left) talks with critical care nurse...

Some people may have health complaints or challenges that the car needs to be aware of as its taking them to the mall, she said.

Kaiser Permanente, one of the largest health systems in Northern California, recently set up a futuristic mock exam room where patients can sit in front of a computer screen to talk to a doctor remotely while using a stethoscope, digital thermometer and otoscope to check their own symptoms under the guidance of the physician. Kaiser CEO Bernard Tyson has personally participated in the experiment.

That is the future being able to provide a great health care service without someone having to get up and go all the way across town for that kind of medical visit, Tyson said. All these things represent the moving away from the hospital being the centerpiece of health care.

Critical care nurse Karen Laberge monitors vitals of present ICU patients at California Pacific Medical Center's eICU hub.

Critical care nurse Karen Laberge monitors vitals of present ICU...

Last year, 70 million interactions between Kaiser patients and their primary care doctor were done by secure email, video conference and other remote tools.

Worldwide revenue for telehealth devices and services is expected to hit $4.5 billion next year, compared to $441 million in 2013, according to the business analytics firm IHS Technology. During the same period, the number of people using telehealth services each year is projected to grow from 350,000 to 7 million.

I dont think well get to a point where well never see a doctor, but a large percentage (of doctors) will be seeing patients remotely in the future, said Dr. David Tong, director of the telestroke program at California Pacific Medical Center in San Francisco. His program connects his vascular neurology practice with 20 other hospitals from the Oregon border to Visalia, so hospital physicians can seek his help in treating a stroke patient. Tong does a visual assessment of the patients using technology similar to Skype.

Tong has led the program since its inception a decade ago, when just two hospitals were in the telestroke network, and the concept of talking to a doctor through a screen seemed foreign to many patients. Today, its commonplace People think, If I do this all the time with my friends, Ill do it with my doctors too. Whats the difference? Tong said.

Despite the promise of remote medical care, though, many traditional barriers to health care remain. Wealth, geography and access to insurance are privileges that no app or technological advancement can replace.

The major stumbling block right now is financial, said Tong. Right now, most insurance doesnt pay for telemedicine in a very efficient way. That blocks some people from doing it.

Medicare and Medi-Cal, for example, limit their reimbursement for telemedicine services to psychiatry and to patients who live in rural areas, Tong said.

There may also be drawbacks to receiving care remotely, which reduces the need for physical interaction. Studies have shown that human touch reduces stress, helps premature babies grow faster and improves the lives of nursing home residents.

A patient's chest x-rays shown on a monitor at California Pacific Medical Center's eICU hub.

A patient's chest x-rays shown on a monitor at California Pacific...

But in another promising development, medicine is also moving in the direction of preventing diseases before they even cause any symptoms. Efforts by genetic testing firms to screen large populations coupled with research in gene therapy and gene editing will give people more information than ever before on their genetic makeup.

As soon as five years from now, everyone who wants to be sequenced will have been sequenced, said Dr. Jill Hagenkord, chief medical officer at Color Genomics, a Burlingame company that sells a $249 test that analyzes 30 genes associated with common hereditary cancers including breast, ovarian and pancreatic cancer. People can buy the test directly from Color or on Amazon, but they must submit their health information and have a physician review it and order the test before Color will analyze the sample.

Whether thats newborn screening in the hospital system or in a research setting ... sequencing data will just exist, Hagenkord said.

Color is already taking steps toward population screening, working with 40 large self-insured employers including Visa and Salesforce which collectively cover tens of thousands of people that subsidize or pay for the test for employees and spouses.

Using gene testing as a preventive tool doesnt take the medical professional out of the equation, but maybe youll just have a conversation earlier with your doctor, about getting a colonoscopy sooner or making choices that may reduce your risk of certain cancers, Hagenkord said.

Meanwhile, researchers are working to bring gene therapy from the clinical trial stage to the real world to treat retinal disease and hemophilia though treatments are not yet available commercially, said Dr. Chris Haskell, who leads Bayer Corp.s West Coast Innovation Center. Bayer has a joint venture with CRISPR Therapeutics which uses the gene-editing tool known as CRISPR to develop and market therapeutics for blood disorders, blindness and congenital heart disease.

With gene therapies, the industry is moving ahead very rapidly in clinical development toward bringing these to patients very soon, Haskell said. Gene editing is still a number of years away behind gene therapy, but has promise for being able to treat many more diseases.

Gene editing is considered a subset of gene therapy. Gene therapy consists of adding a missing part of a persons DNA, typically through an injection of an engineered virus that carries the replacement gene. With the blood-clotting disorder hemophilia A, patients are missing a blood-clotting protein called factor VIII. This protein is injected and, over the course of the next several days or weeks, the cells start producing the clotting factor and allow the circulatory system to clot normally.

The trailblazing is happening with hemophilia because we understand the disease, Haskell said. But theres a huge promise for bringing therapies to patients around the world, especially kids with metabolic disorders who have no good therapy.

Gene editing makes it possible to modify the genetic code and the applications seem limitless.

This opens up a whole new realm of ways to treat diseases in that we can turn things on and off, take things out, Haskell said. With gene therapy, we have the hammer. Now we have the whole toolbox. However, were still learning how to use all these tools.

And the workshop for those tools? It will be anywhere but your old, familiar doctors office.

Catherine Ho is a San Francisco Chronicle staff writer. Email: cho@sfchronicle.com Twitter: @Cat__Ho

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Why doctors' offices could become obsolete - San Francisco Chronicle

(Credit: nenetus/Shutterstock)

A rare mutation that nearly killed a young girl has revealed insights into the common cold.

Researchers from theNational Institute of Allergy and Infectious Diseases conducted a genetic analysis of a child who had been laid low by repeated boutsof rhinovirus (the virus that causes colds) and influenza infections severe enough toplace her on life support. By combing through her genome, they found a single mutation that they say obstructed her bodys natural disease-fighting pathway. The finding not only helped to solve a medical mystery, it could also give us new assets in the fight against common viral infections.

When a virus enters our cells and begins churning out copies of itself, the cells normally react by releasing signaling proteins called interferons. This cellular distress signal alerts other cells in the vicinity to be on guard against the virus, and is a crucial step in our bodies ability to fight disease. This particular patient, however, had a mutation that prevented her cells from recognizing and responding to rhinovirus, allowing it to proliferate throughout her body unchecked.

Her health eventually improved somewhat as her immune system grew stronger, although at five years of age, she is still at risk.

Researchers were already aware that the misbehaving protein called MDA5 was involved with signaling the immune system when a virus began to spread, but their findings help to pin down an explicit link to rhinovirus infections. It gives us more insight into how the common cold is contracted and spreads through the body, which is helpful, given that we still dont have an effective means of preventing the virus. Although colds arent normally seen as a serious disease, they can be deadly for individuals with asthma, COPD and other lung diseases, as well as the elderly.

While the research here, published Monday in the Journal of Experimental Medicine,was confined to a single person with a rare mutation, the benefits could extendmuch further. Up until they encountered an individual with this mutation, the researchers were unaware of the role MDA5 proteins play in helping to protect us against colds, a discovery that could guide treatments in the future. The concept is similar to how researchers working with so-called knockout mice with specific genes disabled uncover the secrets of our genomes. Sometimes, its only by seeing what goes wrong when a gene is missing that we can figure out what it does. Cases such as this highlight the value of rare occurrences in medicine, according to study lead author Helen Su.

Its not just because were trying to treat the rare people, but because they give us an insight that would not be easily obtained by studying lots of normal people, she says. They can actually be very instructive.

Though this is the only confirmed MDA5 mutation of this nature, more likely exist, Su says. She and her colleagues also combed through a database of 60,000 genomes looking for similar mutations in the IFIH1 gene that codes for the protein. They found several variations that they say could lead to impaired immune functions, although none seemed to materialize in these individuals, indicating that multiple factors are likely at play.

As for the rest of us, dont worry, the mutation is rare, and if youre reading this youre almost certainly fine. Su emphasizes that colds arent aproblem for healthy individuals, and only become a problem when other issues arise.

In some rare cases, however, all it takes is a single genetic variation for a common illness to take a deadly turn.

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A Rare Genetic Mutation Reveals Secrets of the Common Cold - Discover Magazine (blog)

Researchers say they discovered hundreds of mutations during a gene editing experiment, casting doubt on CRISPR's safety and precision.

CRISPR gene editing technology has tantalized the public with its potential to cure disease.

However, new research suggests it could be more dangerous and less precise than previously believed.

CRISPR-Cas9 was discovered in 2012 by University of California molecular biologist Jennifer Doudna and her colleagues. It allows for genetic editing by snipping out small bits of defective or harmful DNA and replacing it.

Gene editing has existed since the 1970s, but CRISPR-Cas9 has reinvented it as a precise, accessible technology.

The potential applications seem almost limitless.

This year, Dr. Edze Westra of the University of Exeter, told the Independent that he expects the technology to be used to cure all inherited diseases, to cure cancers, to restore sight to people by transplanting genes.

Read more: Scientists find gene editing with CRISPR hard to resist

Still in its infancy, CRISPR-Cas9 has yet to deliver on these promises, in humans anyway.

One of the key talking points of CRISPR-Cas9 has been its precision its ability to accurately edit small sections of DNA without affecting nearby sections.

However, a new study from Columbia University says that CRISPR-Cas9 can introduce hundreds of unexpected mutations into the genome beyond what was intended.

We feel its critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, said co-author Dr. Stephen Tsang, a professor at Columbia University Medical Center, in a press release.

Tsang and his team discovered the mutations while conducting research on mice, using CRISPR-Cas9 to correct a gene that caused blindness.

The technology worked effectively in curing the blindness, but when the researchers later looked at the genome of the mice, they said they found additional, unintended mutations.

Despite this, the mice appeared to be in fine health.

We did not see any observable complications in the mice, despite having all these extra CRISPR-related mutations, Tsang told Healthline.

Sheila Jasanoff, professor of science and technology studies at Harvard University, told Healthline that precision can have a slippery definition in biotechnology.

Genetic engineering was also sold some 40 years ago as a highly precise technique. Now, CRISPR is being heralded as even more precise, she said.

Undoubtedly, there is some truth in that claim ... But we also know from older genetic engineering techniques that very precise interventions into one part of a genome can produce unexpected side effects or off-target impacts that scientists were not expecting, Jasanoff added.

Read more: CRISPR gene editing and cancer treatment

Tsang frames the message of his research in two ways.

First, he hopes that his work will bring a newfound awareness to the potential side effects caused by CRISPR.

Although the mutations he and his team observed did not appear to have any malignant effects, they should be a wake-up call for researchers.

Secondly, Tsang says that no matter what kind of medicine or treatment is being used, there is the potential for side effects.

If we apply CRISPR, its just like any other intervention medicine. There is always off-targeting and risks and benefits, he says.

Jasanoff is more tempered in her assessment of the risk vs. reward of CRISPR.

The assumption that there are untold benefits in store long before the work has been done to establish how a new technology actually will have an impact on any disease is a typical example of the hype that surrounds new and emerging technologies, she said.

Tsangs research offers no hard answers to the larger questions of efficacy, risk, and benefit of using CRISPR on humans.

Lets not go overboard, said Pete Shanks, a consultant who is an expert on genetics. Three blind mice dont prove much.

Tsangs research does provide some cautionary insight into how research must be conducted in order to make the technology safer.

Currently most studies of off-target mutations depend on computer algorithms to locate and examine affected areas. Tsang and his team say that this isnt sufficient when using live specimens.

These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals, Alexander Bassuk, professor of pediatrics at the University of Iowa, and co-author of the study, said in a press release.

Researchers who arent using whole genome sequencing to find off-target effects may be missing potentially important mutations, Tsang said.

Read more: Gene editing could be used to battle mosquito-borne disease

This study comes at an important time.

China has begun its first round of human testing using CRISPR-Cas9.

The United States is due to start its own tests next year.

The research field is moving quickly perhaps too quickly.

We hope our findings will encourage others to use whole genome sequencing as a method to determine all the off-target effects of their CRISPR techniques and study different versions for the safest, most accurate editing, Tsang said.

Jasanoff is much blunter.

We should put aside the notion the benefits of CRISPR are already proven, and all we need to worry about is risks, she said.

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Is CRISPR Gene Editing Moving Ahead Too Quickly? - Healthline

MONDAY, June 5, 2017 (HealthDay News) -- Genetically tuning a person's own immune cells to target cancer appears to provide long-lasting protection against a blood cancer called multiple myeloma, an early trial from China shows.

The treatment, called CAR T-cell therapy, caused 33 out of 35 patients with recurring multiple myeloma to either enter full remission or experience a significant reduction in their cancer.

The results are "impressive," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"These are patients who have had prior treatment and had their disease return, and 100 percent of the patients are reported to have had some form of meaningful response to these cells that were administered," Lichtenfeld said.

The new therapy is custom-made for each patient. Doctors collect the patient's own T-cells -- one of the immune system's main cell types -- and genetically reprogram them to target and attack abnormal multiple myeloma cells.

Lead researcher Dr. Wanhong Zhao likened the process to fitting immune cells with a GPS that steers them to cancer cells -- making them into professional killers that never miss their target.

Zhao is associate director of hematology at the Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, China.

CAR T-cell therapy is promising because the genetically altered T-cells are expected to roost in a person's body, multiplying and providing long-term protection, Lichtenfeld said.

"The theory is they should attack the tumor and continue to grow to become a long-term monitoring and treatment system," Lichtenfeld said. "It's not a one-shot deal."

The technology represents the next step forward in immunotherapy for cancer, said Dr. Michael Sabel, chief of surgical oncology at the University of Michigan.

"Immunotherapy is now really providing hope to a lot of patients with cancers that were not really responding to our standard chemotherapies," Sabel said.

CAR T-cell therapy previously has been used to treat lymphoma and lymphocytic leukemia, Lichtenfeld said.

Zhao and his colleagues decided to try the therapy to treat multiple myeloma. They re-engineered the patients' T-cells and then reintroduced them to the body in three infusions performed within one week.

Multiple myeloma is a cancer that occurs in plasma cells, which are mainly found in bone marrow and produce antibodies to fight infections. About 30,300 people will likely be diagnosed with multiple myeloma this year in the United States, researchers said in background notes.

"Multiple myeloma is a disease that historically was fatal in the course of a couple of years," Lichtenfeld said. During the past two decades, new breakthroughs have extended survival out 10 to 15 years in some patients, he noted.

To date, 19 of the first 35 Chinese patients have been followed for more than four months, researchers report.

Fourteen of those 19 patients have reached the highest level of remission, researchers report. There hasn't been a relapse among any of these patients, including five followed for more than a year.

"That's as far as you can go in terms of driving down the amount of tumor that's in the body," Lichtenfeld said.

Out of the remaining five patients, one experienced a partial response and four a very good response, researchers said.

However, about 85 percent of the patients experienced cytokine release syndrome (CRS), a potentially dangerous side effect of CAR T-cell therapy.

Symptoms of cytokine release syndrome can include fever, low blood pressure, difficulty breathing, and impaired organ function, the researchers said. However, most of the patients experienced only transient symptoms, and "now we have drugs to treat it," Lichtenfeld said.

History suggests the therapy will cost a lot if it receives approval, Lichtenfeld said. However, prior to approval, much more research will be needed, he added.

The Chinese research team plans to enroll a total of 100 patients in this clinical trial at four hospitals in China. They also plan a similar clinical trial in the United States by 2018, Zhao said.

The study was funded by Nanjing Legend Biotech Co., the Chinese firm developing the technology.

The findings were presented Monday at the American Society of Clinical Oncology annual meeting, in Chicago. Data and conclusions presented at meetings are usually considered preliminary until published in a peer-reviewed medical journal.

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Gene-Based Therapy May Thwart a Tough Blood Cancer - Montana Standard