June 1, 2017 This microscopic image of fibroblast cells shows the induction of cell fusion by a newly described gene and its protein, called myomerger. Multi-nucleus cells expressing genes needed to form skeletal muscle can be seen in flower-like clumps forming as cells fuse together. Reporting results in Nature Communications, the researchers seek ways to develop regenerative therapies for muscle disorders by getting stem cells to fuse and form functioning skeletal muscle tissues. Credit: Cincinnati Children's

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature Communications reports scientists identify a new gene essential to this process, shedding new light on possible new therapeutic strategies.

Led by researchers at the Cincinnati Children's Hospital Medical Center Heart Institute, the study demonstrates the gene Gm7325 and its protein - which the scientists named "myomerger" - prompt muscle stem cells to fuse and develop skeletal muscles the body needs to move and survive. They also show that myomerger works with another gene, Tmem8c, and its associated protein "myomaker" to fuse cells that normally would not.

In laboratory tests on embryonic mice engineered to not express myomerger in skeletal muscle, the animals did not develop enough muscle fiber to live.

"These findings stimulate new avenues for cell therapy approaches for regenerative medicine," said Douglas Millay, PhD, study senior investigator and a scientist in the Division of Molecular Cardiovascular Biology at Cincinnati Children's. "This includes the potential for cells expressing myomaker and myomerger to be loaded with therapeutic material and then fused to diseased tissue. An example would be muscular dystrophy, which is a devastating genetic muscle disease. The fusion technology possibly could be harnessed to provide muscle cells with a normal copy of the missing gene."

Bio-Pioneering in Reverse

One of the molecular mysteries hindering development of regenerative therapy for muscles is uncovering the precise genetic and molecular processes that cause skeletal muscle stem cells (called myoblasts) to fuse and form the striated muscle fibers that allow movement. Millay and his colleagues are identifying, deconstructing and analyzing these processes to search for new therapeutic clues.

Genetic degenerative disorders of the muscle number in the dozens, but are rare in the overall population, according to the National Institutes of Health. The major categories of these devastating wasting diseases include: muscular dystrophy, congenital myopathy and metabolic myopathy. Muscular dystrophies are a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement. The most common form is Duchenne MD.

Molecular Sleuthing

A previous study authored by Millay in 2014 identified myomaker and its gene through bioinformatic analysis. Myomaker is also required for myoblast stem cells to fuse. However, it was clear from that work that myomaker did not work alone and needed a partner to drive the fusion process. The current study indicates that myomerger is the missing link for fusion, and that both genes are absolutely required for fusion to occur, according to the researchers.

To find additional genes that regulate fusion, Millay's team screened for those activated by expression of a protein called MyoD, which is the primary initiator of the all the genes that make muscle. The team focused on the top 100 genes induced by MyoD (including GM7325/myomerger) and designed a screen to test the factors that could function within and across cell membranes. They also looked for genes not previously studied for having a role in fusing muscle stem cells. These analyses eventually pointed to a previously uncharacterized gene listed in the database - Gm7325.

Researchers then tested cell cultures and mouse models by using a gene editing process called CRISPR-Cas9 to demonstrate how the presence or absence of myomaker and myomerger - both individually and in unison - affect cell fusion and muscle formation. These tests indicate that myomerger-deficient muscle cells called myocytes differentiate and form the contractile unit of muscle (sarcomeres), but they do not join together to form fully functioning muscle tissue.

Looking Ahead

The researchers are building on their current findings, which they say establishes a system for reconstituting cell fusion in mammalian cells, a feat not yet achieved by biomedical science.

For example, beyond the cell fusion effects of myomaker and myomerger, it isn't known how myomaker or myomerger induce cell membrane fusion. Knowing these details would be crucial to developing potential therapeutic strategies in the future, according to Millay. This study identifies myomerger as a fundmentally required protein for muscle development using cell culture and laboratory mouse models.

The authors emphasize that extensive additional research will be required to determine if these results can be translated to a clinical setting.

Explore further: Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

More information: Nature Communications (2017). DOI: 10.1038/NCOMMS15665

Adding just the right mixture of signaling moleculesproteins involved in developmentto human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage ...

A team led by Jean-Franois Ct, researcher at the IRCM, identified a ''conductor'' in the development of muscle tissue. The discovery, published online yesterday by the scientific journal Proceedings of the National ...

Athletes, the elderly and those with degenerative muscle disease would all benefit from accelerated muscle repair. When skeletal muscles, those connected to the bone, are injured, muscle stem cells wake up from a dormant ...

Johns Hopkins researchers report they have inadvertently found a way to make human muscle cells bearing genetic mutations from people with Duchenne muscular dystrophy (DMD).

Duchenne muscular dystrophy is a chronic disease causing severe muscle degeneration that is ultimately fatal. As the disease progresses, muscle precursor cells lose the ability to create new musclar tissue, leading to faster ...

Researchers at Sanford Burnham Prebys Medical Research Institute (SBP) have conclusively identified the protein complex that controls the genes needed to repair skeletal muscle. The discovery clears up deep-rooted conflicting ...

A University of California, Berkeley, study of mice reveals, for the first time, how puberty hormones might impede some aspects of flexible youthful learning.

The bacteria in a child's gut appears to be influenced as early as its first year by ethnicity and breastfeeding, according to a new study from McMaster University.

The human body runs according to a roughly 24-hour cycle, controlled by a "master" clock in the brain and peripheral clocks in other parts of the body that are synchronized according to external cues, including light. Now, ...

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature ...

Cholesterol, a naturally occurring compound at the lung surface, has been shown to have a clear effect on the properties of this nanoscale film that covers the inside of our lungs. Cholesterol levels in this system may affect ...

Researchers from Monash University have developed a new drug delivery strategy able to block pain within the nerve cells, in what could be a major development of an immediate and long lasting treatment for pain.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read more from the original source:
One gene closer to regenerative therapy for muscular disorders - Medical Xpress

Making Public Data Public The Scientist Indeed, we try to keep track, but sometimes it's six months or even two years that a paper is bouncing around from journal to journal, says genetic medicine researcher Ronald Crystal of Weill Cornell Medicine in New York who at the time of the ...

Continued here:
Making Public Data Public - The Scientist

It may sound like a script for a science fiction movie, but scientists have created the worlds first mutant ants.

Two independent research teams have harnessed the gene editing technology CRISPR to genetically alter the ants. In one study, researchers at Rockefeller University modified a gene essential for sensing the pheromones that ants use to communicate. Experts say that the resulting deficiencies in the ants social behaviors and their ability to survive in a colony, sheds light on social evolution.

It was well known that ant language is produced through pheromones, but now we understand a lot more about how pheromones are perceived, said Daniel Kronauer, head of Rockefeller Universitys Laboratory of Social Evolution and Behavior, in a statement. The way ants interact is fundamentally different from how solitary organisms interact, and with these findings we know a bit more about the genetic evolution that enabled ants to create structured societies.

GENE EDITING BREAKTHROUGH COULD PAVE WAY FOR PIG-TO-HUMAN ORGAN TRANSPLANTS

CRISPR, which has been compared to a pair of molecular scissors, lets scientists alter or replace specific sections of DNA.

Scientists used CRISPR to disrupt a gene known asOrco in the clonal raider ant,species Ooceraea biroi, but then faced the challenge of keeping the mutant ants alive. We had to convince the colonies to accept the mutants. If the conditions werent right, the worker ants would stop caring for larvae and destroy them, said Rockefeller University graduate fellow Waring Trible, in the statement. Once the ants successfully made it to the adult phase, we noticed a shift in their behavior almost immediately.

While ants typically travel single file, researchers noticed that the mutant ants couldnt fall in line, along with other behavioral abnormalities.

DNA BREAKTHROUGH: SCIENTISTS REPAIR GENES IN HUMAN EMBRYOS TO PREVENT INHERITED DISEASES

The results of the study are published in the journal Cell.

This image shows a Harpegnathos saltator worker ant in the process of stinging a cricket to paralyze it and drag it into the nest as part of its hunting duties. (Credit: Brigitte Baella)

A separate study, also published in the journal Cell, saw scientists target the Orco gene in the Indian jumping ant,Harpegnathos saltator. Experts note that the Indian jumping ant is unlike other ant species because only the queen can mate and pass genes onto the next generation. However, any adult female worker of the species can become a pseudo queen in the queens absence.

The second study was led by researchers from New York University, NYU School of Medicine, Arizona State University, the University of Pennsylvania and Vanderbilt University.

Ant queens suppress the ability of female workers to mate and lay eggs, although if the queen is removed, the most aggressive females, after winning a series of antenna duels with rivals, can go on to lay eggs.

DNA DISCOVERY UNRAVELS THE MYSTERY OF EARLY GREEK CIVILIZATIONS

The study engineered three mutant ants to lack the Orco gene. Without the gene, females cannot process pheromones, making them less likely to engage in dueling.

"While ant behavior does not directly extend to humans, we believe that this work promises to advance our understanding of social communication, with the potential to shape the design of future research into disorders like schizophrenia, depression or autism that interfere with it," said Claude Desplan, professor at NYU's Department of Biology, and one of the reports authors, in a statement.

In a third related study by the University of Pennsylvania, scientists injected the brain chemical corazonin into ants transitioning to become a pseudo-queen, which simulated worker-like hunting behaviors, while inhibiting pseudo-queen behavior, such as dueling and laying eggs.

DNA DISCOVERY IDENTIFIES LIVING DESCENDANTS OF BIBLICAL CANAANITES

These results are also published in the journal Cell.

Gene editing has been generating plenty of buzz recently. Earlier this week, scientists announced the elimination of viruses in pigs that could be harmful to people, utilizing the CRISPR technology. The discovery could potentially lay the foundations for pig-to-human organ transplants.

GENE EDITING BREAKTHROUGH COULD PAVE WAY FOR PIG-TO-HUMAN ORGAN TRANSPLANTS

In another project, researchers used gene-editing to correct a disease-causing gene mutation in human embryos, preventing the mutation from passing to future generations. In the stunning discovery, a research team led by Oregon Health and Science University reported that embryos can fix themselves if scientists jump-start the process early enough.

Follow James Rogers on Twitter @jamesjrogers

Originally posted here:
Scientists create world's first mutant ants with gene editing technology - Fox News

Gene sequencing study reveals unusual mutations in endometriosis Science Daily Using gene sequencing tools, scientists from Johns Hopkins Medicine and the University of British Columbia have found a set of genetic mutations in samples from 24 women with benign endometriosis, a painful disorder marked by the growth of uterine ... and more »

Excerpt from:
Gene sequencing study reveals unusual mutations in endometriosis - Science Daily

May 09, 2017 09:13 ET | Source: Admera Health, LLC

SOUTH PLAINFIELD, N.J. and ROCHESTER, N.Y., May 09, 2017 (GLOBE NEWSWIRE) -- Today, the University of Rochester School of Medicine and Dentistry and Admera Health announced that enrollment had commenced in a randomized clinical study evaluating the use of pharmacogenomics to guide pain management decisions related to acute dental surgery. Specifically, the study is seeking to determine if a preoperative chair-side pharmacogenomic algorithm can significantly enhance the efficacy of surgical pain management and to characterize the association between gene-drug interactions and clinical outcomes.

Admera Health, a molecular diagnostic company, will extract and sequence DNA samples provided by the University of Rochester. Sequencing will utilize Admeras PGxOne Plus test, a 50 gene Next Generation Sequencing panel that interrogates nearly 200 different variants and provides recommendations for over 220 drugs based on an individuals unique genetic makeup.

It is well understood in the medical community that most acute surgical pain methods have shown inconsistent effects on pain relief and rely excessively on opioid use, which has associated dependency issues, as stated by Admera CEO and President Guanghui Hu. With the implementation of our PGxOne Plus test, we are confident that this study will demonstrate improved patient outcomes, similar to the way pharmacogenomics has been clinically validated in other therapeutic areas such as cardiovascular health, oncology, and psychiatric care. That is why we are excited to be working with the University of Rochester for this study.

According to the CDC, opioid-involved deaths continue to increase and have reached epidemic status. In March, a United States Senate committee opened a probe into the practices of the top manufacturers of opioid drugs.

About Admera Health

Admera Health is a CLIA-certified and CAP-accredited advanced molecular diagnostics company focused on personalized medicine, non-invasive cancer testing, digital health, and providing research use only services. Research and development efforts are dedicated to developing cutting-edge diagnostics that span the continuum of care. Utilizing next generation technology platforms and advanced bioinformatics, Admera Health seeks to redefine disease screening, diagnosis, treatment, monitoring, and management through its innovative, personalized solutions. It is our mission to deliver transformative, valuable solutions for patients, physicians, and clinical researchers. We are committed to improving the health and well-being of our global community through the direct delivery of personalized, medically actionable results.

Related Articles

South Plainfield, New Jersey, UNITED STATES

http://www.admerahealth.com/

Admera Health, LLC Logo

LOGO URL | Copy the link below

Formats available:

More:
University of Rochester School of Medicine and Dentistry Collaborate with Admera Health in a Clinical Study ... - GlobeNewswire (press release)

What happened

Shares of gene editing pioneer Editas Medicine (NASDAQ:EDIT) dropped nearly 16% today after a new study published in Nature Methods drew attention to unintended effects of using the highly touted genetic engineering tool known as CRISPR. Shares of genome-editing peers CRISPR Therapeutics (NASDAQ:CRSP) and Intellia Therapeutics (NASDAQ:NTLA) were down as much as 6.9% and 14.9%, respectively, on the news.

The study, conducted by a team from Columbia University Medical Center, provided data showing that the technology can "introduce hundreds of unintended mutations into the genome," according to Genetic Engineering & Biotechnology News. That contradicts one of the better-known characteristics of CRISPR: precision.

Simply put, it's not sitting well with investors, who are (in knee-jerk fashion) adjusting the value placed on early-stage platforms, especially Editas Medicine, which will be the first of the group to enter clinical trials. As of 3:31 p.m. EDT, the stock had settled to a 11.3% loss.

Image source: Getty Images.

The study is among the first to quantify the specificity of CRISPR tools, which work by delivering gene editing enzymes to specific parts of the genome through the use of synthetic guide RNAs. Or that's how they're supposed to work. The authors of the study show that although intended edits can be made with respectable efficiency, such as correcting a mutation in a gene that causes blindness in mice, there are also unintended secondary edits made to the genome.

This may seem like a bombshell report, but it's a matter of optics. Researchers have never shied away from the reality that CRISPR gene editing tools can stray off target and make unintended edits to genomes in mammalian cells (i.e., humans). Many labs -- including Editas Medicine, CRISPR Therapeutics, and Intellia Therapeutics -- are working on increasing the efficiency and specificity of the technology. This is how science works. By quantifying these off-target mutations, which the paper attempted to do, researchers can begin to better understand how to improve the technology.

Investors and traders did not take the same cool-headed approach to the news, instead giving into a knee-jerk reaction to adjust the value of each pre-clinical technology platform. While off-target edits could prove troublesome for a CRISPR therapeutic used in humans, it's important to remember that there are currently no clinical trials underway in the United States. Editas Medicine will become the first to initiate a clinical trial later this year.

The sharp contrasts in reactions from researchers and investors is likely driven by how CRISPR is perceived by the media. Unfortunately, there is a generous amount of hyped-up science journalism that sticks to simple narratives -- "CRISPR has arrived and will cure all diseases!" -- instead of more nuanced takes that give equal weight to each current obstacles and future potential facing an emerging technology. Just remember: Biology is never quite so simple.

The results from the study don't really change anything, except for bringing more attention to the already existent clinical risk inherent to the development of early-stage CRISPR therapeutics. There is still plenty of work and new technology left to be developed before gene editing fulfills its promise in treating and curing human diseases. Hopefully, this can be a long-term positive for investors in CRISPR stocks by forcing them to listen to the fundamental hurdles for the technology. Hopefully.

Maxx Chatsko has no position in any stocks mentioned. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy.

Go here to see the original:
Here's Why Editas Medicine Fell as Much as 15.7% Today - Motley Fool

Doctors have long known that genetics can predispose some people to gain weight despite a healthy lifestyle while others seemingly never gain an ounce no matter how much they eat. A new study sheds light on how people can counteract their genetic makeup, even if it's in their DNA to put on more weight than others.

Researchers from University of North Carolina Chapel Hill, the University of Copenhagen and other institutions conducted a meta-analysis examining 60 past genetic studies to see if physical activity could mitigate the effects a genetic predisposition to weight gain.

"Decline in daily physical activity is thought to be a key contributor to the global obesity epidemic," the authors wrote. However, they explained that genetic make-up may also play a role in weight gain for people who are not physically active.

They screened for 2.5 million genetic variants in 200,452 adults and also separated the subjects between those who were physically active -- about 77 percent -- and those who were physically inactive, about 23 percent. The researchers then looked at different markers that would indicate if a person was overweight including their body-mass index, waist circumference and hip-to-waist ratio.

They found those with a genetic variation that predisposed them to gain weight -- called an FTO gene -- had the ability counteract the effects that gene through exercise. By looking at the data they found that those with the FTO gene who were physically active were able to reduce the weight-gain effects associated with the gene by about 30 percent.

Dr. Goutham Rao, chairman of Family Medicine and Community Health at University Hospitals Cleveland Medical Center, said this type of research is key in helping patients better understand their weight and health.

"Despite that sort of bad luck of having a genetic predisposition to obesity if you are physically active ... you're not going to reduce risk of obesity entirely but you reduce it significantly," Rao said.

The mechanism that leads to people with FTO to be predisposed to gain weight is still not fully understood, but Rao said it's key to give people encouragement that taking healthy steps has an effect even if they haven't reached their goal weight.

"The message is to be sympathetic," Rao said. Explaining he tells frustrated patients, "if you weren't doing your best you would weigh a lot more and be much less healthy."

Dr. Kevin Niswender, associate professor of medicine, molecular physiology and biophysics at Vanderbilt University Medical Center, said the study took on the "really interesting question" of if people can counteract their genetics through their lifestyle.

"This study definitively confirms that lifestyle has an impact," he said.

During their research the team also discovered 11 new genetic variants that likely predispose a person to weight gain and they said more may be found through similar studies.

"In future studies, accounting for physical activity and other important lifestyle factors could boost the search for new obesity genes," said Mariaelisa Graff of the University of North Carolina at Chapel Hill, the lead author of the study. "To identify more genes whose effects are either dampened or amplified by physical activity, we need to carry out larger studies with more accurate measurement of physical levels."

Niswender said finding new variants that indicate predisposition for weight gain can help give a better understanding of the complex mechanisms behind obesity.

"For a long time we've been searching for this gene, the gene that causes obesity and it's just not like that," Niswender."there are a bunch of genes that cause obesity and the effect of each gene variant is really quite small."

Graff said more study should need to be done to get more accurate measurements of the participants' physical activity. The researchers classified those as having a sedentary job, commute and leisure time as "inactive" while everyone else was declared physically active. Additionally, the study was done primarily in people of European descent, so the findings may not be be easily extrapolated to other groups.

Read this article:
Exercise can help offset effects of 'fat gene,' study finds - ABC News

Visit the News Hub

Goal is vaccine that targets inflammation in joints

Using CRISPR technology, a team of researchers led by Farshid Guilak, PhD, at Washington University School of Medicine in St. Louis, rewired stem cells' genetic circuits to produce an anti-inflammatory arthritis drug when the cells encounter inflammation. The technique eventually could act as a vaccine for arthritis and other chronic conditions.

Using new gene-editing technology, researchers have rewired mouse stem cells to fight inflammation caused by arthritis and other chronic conditions. Such stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy),develop into cartilage cells that produce a biologic anti-inflammatory drug that, ideally, will replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation.

The cells were developed at Washington University School of Medicine in St. Louis and Shriners Hospitals for Children-St. Louis, in collaboration with investigators at Duke University and Cytex Therapeutics Inc., both in Durham, N.C. The researchers initially worked with skin cells taken from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation.

The research is availableonline April 27 in the journal Stem Cell Reports.

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, PhD, the papers senior author and a professor of orthopedic surgery at Washington University School of Medicine. To do this, we needed to create a smart cell.

Many current drugs used to treat arthritis including Enbrel, Humira and Remicade attack an inflammation-promoting molecule called tumor necrosis factor-alpha (TNF-alpha). But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, said Guilak, also a professor of developmental biology and of biomedical engineering and co-director of Washington Universitys Center of Regenerative Medicine. If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint.

As part of the study, Guilak and his colleagues grew mouse stem cells in a test tube and then used CRISPR technology to replace a critical mediator of inflammation with a TNF-alpha inhibitor.

Exploiting tools from synthetic biology, we found we could re-code the program that stem cells use to orchestrate their response to inflammation, said Jonathan Brunger, PhD, the papers first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

Over the course of a few days, the team directed the modified stem cells to grow into cartilage cells and produce cartilage tissue. Further experiments by the team showed that the engineered cartilage was protected from inflammation.

We hijacked an inflammatory pathway to create cells that produced a protective drug, Brunger said.

The researchers also encoded the stem/cartilage cells with genes that made the cells light up when responding to inflammation, so the scientists easily could determine when the cells were responding. Recently, Guilaks team has begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases.

If the work can be replicated in animals and then developed into a clinical therapy, the engineered cells or cartilage grown from stem cells would respond to inflammation by releasing a biologic drug the TNF-alpha inhibitor that would protect the synthetic cartilage cells that Guilaks team created and the natural cartilage cells in specific joints.

When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation, Guilak explained. We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, its 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.

With an eye toward further applications of this approach, Brunger added, The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine.

Brunger JM, Zutshi A, Willard VP, Gersbach CA, Guilak F. Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs. Stem Cell Reports. April 27, 2017.

This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging of the National Institutes of Health (NIH), grant numbers AR061042, AR50245, AR46652, AR48182, AR067467, AR065956, AG15768, OD008586. Additional funding provided by the Nancy Taylor Foundation for Chronic Diseases; the Arthritis Foundation; the National Science Foundation (NSF), CAREER award number CBET-1151035; and the Collaborative Research Center of the AO Foundation, Davos, Switzerland.

Authors Farshid Guilak, and Vincent Willard have a financial interest in Cytex Therapeutics of Durham, N.C., which may choose to license this technology. Cytex is a startup founded by some of the investigators. They could realize financial gain if the technology eventually is approved for clinical use.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

View post:
Stem cells edited to fight arthritis - Washington University School of Medicine in St. Louis

Source: Thinkstock

April 25, 2017 -A team from the University of Virginia School of Medicine has developed a quicker way to examine the impact of gene mutation on patient health, potentially changing the way cancer labs conduct research into precision medicine and personalized therapies.

The methodology, which uses a virus similar to HIV to replace normal genes with specific mutations, may even be speedier and more cost effective than the CRISPR gene editing technology that currently forms the basis for much of the industrys cutting-edge genomics work.

"Every patient shouldn't receive the same treatment. No way. Not even if they have the same syndrome, the same disease," said UVA researcher J. Julius Zhu, PhD, who led the team that created the new technique. "It's very individual in the patient, and they have to be treated in different ways."

The process of understanding and testing a specific mutations impact on disease development and the usefulness of particular therapies has thus far been slow and painful, said Zhu, who holds positions in UVA's Department of Pharmacology and the UVA Cancer Center.

"You can do one gene and one mutation at a time, he said. Even with the CRISPR [gene editing] technology we have now, it still costs a huge amount of money and time and most labs cannot do it, so we wanted to develop something simple every lab can do. No other approach is so efficient and fast right now.

In addition to ramping up the velocity of studying gene mutations, the new approach may be able to reduce failures in the research process by giving researchers a more sensitive, targeted way to stimulate gene activity.

"The problem in the cancer field is that they have many high-profile papers of clinical trials [that] all failed in some way," Zhu said. "We wondered why in these patients sometimes it doesn't work, that with the same drug some patients are getting better and some are getting worse. The reason is that you don't know which drugs are going to help with their particular mutation. So that would be true precision medicine: You have the same condition, the same syndrome, but a different mutation, so you have to use different drugs."

Zhu has already used the method to analyze approximately 50 mutation of the BRaf gene, which has been tied to tumor development and certain neurodevelopmental disorders. He envisions that the technique will also help unlock the secrets of other diseases, such as Alzheimers, cystic fibrosis, and a variety of cancers all of which are top priorities for precision medicine researchers.

As the marketplace for targeted therapies and associated precision medicine technologies approaches the $100 billion mark, techniques that can help cancer researchers accelerate the development of new treatments will continue to be in high demand.

Drastically reducing the time from hypothesis to bedside will likely produce financial benefits for research labs as well as clinical benefits for patients.

You'd need to spend 10 years to do what we are doing in three months, so it's an entirely different scale, said Zhu. Now, hopefully, we can do 40 or 100 of them simultaneously."

Read more from the original source:
UVA Gene Mutation Research Method Speeds Precision Medicine - Health IT Analytics

A recent study from Dr. Song on the topic of research progress on treatment of cancer with Compatibility of Traditional Chinese Medicine establishes that the targeted gene therapy can be effective.

Xiangtan, China (PRWEB) April 15, 2017

Cancer is one of the major life-threatening diseases that people often worry about. People suffering from cancer often undergo traditional treatments, such as surgery, chemotherapy and radiotherapy. However, such treatments could have harmful side effects.

Research from Dr. Song(Dr. Xinping Song) was recently conducted aimed at studying traditional Chinese medicine compatibility with respect to treating prostate cancer. The study reveals that the targeted gene therapy can be an effective way.

The study also points out the targeted gene therapy can be combined with other therapies for a more effective result. However, this therapy is also not mature enough to address all health issues related to the prostatic cancer. In such a scenario, Dr. Song's 3D Prostate Targeted Treatment emerges as an innovative treatment for prostate cancer. The research revealed that the therapy can be combined with local targeted injections. The technique makes the therapy effective and increases its killing effect on cancer cells.

Dr. Song's treatment is based on the direct injection technique of the traditional Chinese medicine system. Dr. Xinping Song acknowledges the findings of the research and also the anti-cancer extract compatibility of the traditional Chinese medicine. In this prostate cancer treatment, patients are given small targeted injections in the affected areas of the prostate to help eliminate causative pathogens and clear the blockage. The injections carry herbal extracts only.

Dr. Song believes that the traditional Chinese anticancer medicine can better interpose with the symptoms of cancer patients. Dr. Song's prostate cancer treatment that follows the principles of traditional Chinese medicine is a clinical breakthrough. This innovative treatment brings more advantages in patients and their family's lives.

At Dr. Song 3D Urology and Prostate Clinic, patients can undergo all types of prostate care and treatment, including the treatment for the prostate cancer. This natural treatment method saves the cost and also meets the patient's requirements. With a non-surgical and quality treatment, patients can gradually improve their health and get rid of their pain and sufferings. To know more about Dr. Song's 3D prostate treatment, one can visit the website http://www.prostatecancer.vip/.

About 3D Urology and Prostate Clinic

The 3D Urology and Prostate Clinic is a premier prostate treatment clinic. The clinic specializes in treating various types of prostate diseases and complications, such as prostatitis, enlarged prostate, benign prostatic hyperlasia (BPH), prostate cancer, seminal vesiculitis, epididymitis,cystitis, prostate blockage and calcification, and chronic pelvic pain syndrome (CPPS), etc. The clinic is a medical clinic, licensed and approved by the Ministry of Health of the People's Republic of China.

For Media Enquiry Contact Person: Alisa Wang Telephone: 86-186-7321-6429 WhatsApp: + 86 -186-73216429 Email: prostatecure3d@gmail.com Website: http://www.prostate-3dcure.com

For the original version on PRWeb visit: http://www.prweb.com/releases/Dr-Song/04/prweb14247467.htm

The rest is here:
Recent advances in experiment and study of prostate cancer targeted therapy - Benzinga

Elizabeth McNally, MD, PhD, director of the Center for Genetic Medicine, delivered the keynote address at Computational Research Day, on human genome sequencing.

Northwesterns 4th Annual Computational Research Day brought together more than 350 faculty members and students to showcase innovative research projects, share recent insights and tools, and strengthen the computational research community throughout the university.

The event, co-sponsored by Feinberg and hosted by Northwestern Information Technology on the Evanston campus, featured presentations, a poster competition, workshops, software demos and group discussions, all centered on leveraging computational methods to answer complex research questions.

Rex Chisholm, PhD, vice dean of Scientific Affairs and Graduate Education, kicked off the conference with an opening address discussing the Northwestern Medicine Enterprise Data Warehouse, which currently holds more than 40 terabytes of clinical and research data.

We are in a completely different world today, where instead of paper records, everybodys health is now captured in an electronic record, said Chisholm, also the Adam and Richard T. Lind Professor of Medical Genetics. The ability to put that data together in a single place and start to think about big data approaches to identifying patterns in that collection of data is a major game-changer.

Chisholm also spoke about the opportunity for merging such health information with data from the NUgene Project, a genomic biobank sponsored by the Center for Genetic Medicine, which has so far sequenced the genomes of more than 1,000 participants. What we really want to do is combine that 100 terabytes of human sequence data with that 40 terabytes of phenotypic data and do an all-by-all comparison, Chisholm said. Its a classic example of a big data opportunity. And its certain that this approach once we figure out how to do it is going to completely revolutionize how we think about disease: how we think about treatment of disease, how we diagnose disease, and how we actually help people prevent disease.

Elizabeth McNally, MD, PhD, director of the Center for Genetic Medicine, delivered a keynote address on human genome sequencing and echoed the opportunities offered by computational research. This really is an area where there has been a lot of need for big data analysis and its definitely not shrinking anytime soon, said McNally, also the Elizabeth J. Ward Professor of Genetic Medicine.

Gary Wilk, a PhD student in the laboratory of Rosemary Braun, PhD, MPH, assistant professor of Preventive Medicine in the Division of Biostatistics, presented at the poster session.

In addition to biomedical research, the conference also highlighted the use of computing in a wide range of other disciplines, from economics and engineering to applied physics and the social sciences. A guest keynote address was delivered by Desmond Patton, PhD, MSW, assistant professor at the Columbia University School of Social Work, who presented on his research into innovating gang violence prevention through qualitative analysis and natural language processing of social media data.

During the speaker sessions, Paul Reyfman, MD, a fellow in pulmonary and critical care, shared his research using transcriptomics to investigate lung diseases.

Gary Wilk, a PhD student in the laboratory of Rosemary Braun, PhD, MPH, assistant professor of Preventive Medicine in the Division of Biostatistics, presented his research, Genetic Variants Modulate Gene Regulation by microRNAs in Cancer, at the events poster session.

We came up with a novel approach using computational methods to integrate many different molecular cancer datasets from large cancer cohorts, and we applied them to find these results, Wilk said.

At the poster session award ceremony, Yoonjung Yoonie Joo, a Health and Biomedical Informatics PhD student in the Driskill Graduate Program (DGP), received second-place for Phenome-wide Association Studies of Polycystic Ovary Syndrome (PCOS), her research with principal investigator M. Geoffrey Hayes, PhD, associate professor of Medicine in the Division of Endocrinology.

Our project identified several significant phenotypic associations with PCOS risk alleles, including diabetes and its comorbidities, Joo said. We suggested novel etiologic pathways underlying PCOS susceptibility loci, enabling biomedical researchers to potentially discover new therapeutic targets for PCOS treatment in the future.

The first-place prize was awarded to Shannon Brady, in the Weinberg College of Arts and Sciences, with third-place going to Jamilah Silver, in the School of Education and Social Policy.

Link:
Scientists and Students Share Insights at Computational Research Day - Northwestern University NewsCenter

Science Daily

Gene-editing alternative corrects Duchenne muscular dystrophy Science Daily ... of the Hamon Center for Regenerative Science and Medicine. Duchenne muscular dystrophy is caused by a mutation to one of the longest genes in the body. When there is a DNA error in the dystrophin gene, the body doesn't make the protein dystrophin, ... and more »

Continued here:
Gene-editing alternative corrects Duchenne muscular dystrophy - Science Daily

Gene therapy is a technique that involves the delivery of nucleic acid polymers into a patients cells as a drug to treat diseases. It fixes a genetic problem at its source. The process involves modifying the protein either to change the genetic expression or to correct a mutation. The emergence of this technology meets the rise in needs for better diagnostics and targeted therapy tools. For instance, genetic engineering can be used to modify physical appearance, metabolism, physical capabilities, and mental abilities such as memory and intelligence. In addition, it is also used for infertility treatment. Gene therapy offers a ray of hope for patients, who either have no treatment options or show no benefits with drugs currently available. The ongoing success has strongly supported upcoming researches and has carved ways for enhancement of gene therapy.

Get Sample of the Report at https://www.reportsweb.com/inquiry&RW00013228326/sample

Leading Gene Therapy Market Players:

The Gene Therapy Market report give a 360-degree holistic view of the market and highlights the key developments, drivers, restraints and future trends with impact analysis of these trends on the market for short-term, mid-term and long-term during the forecast period. In addition, the report also provides profiles of major companies along with detailed SWOT analysis, financial facts and key developments of products/service from the past three years.

The global gene therapy market is segmented based on vector type, gene type, application, and geography. Based on vector type, it is categorized into viral vector and non-viral vector. Viral vector is further segmented into retroviruses, lentiviruses, adenoviruses, adeno associated virus, herpes simplex virus, poxvirus, vaccinia virus, and others. Non-viral vector is further categorized into naked/plasmid vectors, gene gun, electroporation, lipofection, and others. Based on gene type, the market is classified into antigen, cytokine, tumor suppressor, suicide, deficiency, growth factors, receptors, and others. Based on application, the market is divided into oncological disorders, rare diseases, cardiovascular diseases, neurological disorders, infectious disease, and other diseases. Based on region, it is analyzed across North America, Europe, Asia-Pacific, and LAMEA.

Get Discount for This Report @ https://www.reportsweb.com/inquiry&RW00013228326/discount

Table of Contents

Chapter 1: Introduction

Chapter 2: Executive Summary

Chapter 3: Market Overview

Chapter 4: Gene Therapy Market, By Component

Chapter 5: Gene Therapy Market, By Deployment

Chapter 6: Gene Therapy Market, By Organization Size

Chapter 7: Gene Therapy Market, By Application

Chapter 8: Gene Therapy Market, By Region

Chapter 9: Competitive Landscape

To Continue

About ReportsWeb:

ReportsWeb.com is a one stop shop of market research reports and solutions to various companies across the globe. We help our clients in their decision support system by helping them choose most relevant and cost effective research reports and solutions from various publishers. We provide best in class customer service and our customer support team is always available to help you on your research queries.

Contact Us:

Call: +1-646-491-9876Email: [emailprotected]

Continue reading here:
Gene Therapy Market 2020 Increasing Demand with Leading Key Players Bluebird Bio, Editas Medicine, GlaxoSmithKline Plc., Intellia Therapeutics -...

IBS Center for Genome Engineering Director Kim Jin-Soo was recognized for his work on making CRISPR-Cas9 technology more precise and stable.

Asian Scientist Newsroom | April 12, 2017 | Top News

AsianScientist (Apr. 12, 2017) - Professors Kim Jin-Soo and Han Duck-Jong have been honored with the 10th ASAN Award in Basic Medicine and Clinical Medicine, respectively. The ASAN Award for Young Medical Scientists went to Professor Choi Jung-Kyoon at the Department of Bio and Brain Engineering at KAIST and Professor Ahn Jung-Min at the Department of Cardiology at the University of Ulsan College of Medicine.

The basic and clinical medicine winners each received 300 million won (~US$262,000) while the Young Medical Scientists received 50 million won (~US$44,000) at an awards ceremony held on March 20, 2017.

The ASAN Award in Medicine was established in 2007 by the ASAN Foundation to discover and encourage medical scientists who have achieved remarkable accomplishments in the fields of basic and clinical medicine.

Kim, who is the Director of the Institute for Basic Science Center for Genome Engineering, was recognized for his work on making the CRISPR-Cas9 gene editing system more precise and stable.

Using genome editing techniques, I'd like to focus on research which is helpful for patients with genetic and degenerative diseases as well as cancer that are considered intractable. I'll strive harder to develop and commercialize treatments that can directly help such patients, he said.

This honor is largely attributed to the dedicated researchers who have worked with me. I see this award as encouragement for me to contribute to society and humanity by devoting myself more to research.

Source: Institute for Basic Science; Photo: ASAN Foundation. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Read more:
Gene Editing Researcher Receives ASAN Award In Basic Medicine - Asian Scientist Magazine

In Conversation provides a glimpse into the life of an outlier an exceptional person going above and beyond to improve outcomes in their field. In 2019, Professor Kathryn North AC won the prestigious Peter Wills Medal Research Australias flagship award in recognition of her outstanding leadership in genomic medicine, which has helped drive Australias international reputation in this field.

As Director of the Murdoch Childrens Research Institute, Professor North plays a key role in integrating genomic testing and diagnosis into standard health care, with the aim to shorten diagnosis times and increase diagnostic rates to enable early intervention as well as provide access to treatment for people with genetic disorders and cancer. Through her own research, she has worked to identify new disease genes and improve diagnosis, setting the benchmark for ongoing research efforts.

This award, which Im incredibly thrilled to receive, really recognises a range of roles Ive played not just as an individual researcher but as part of the efforts of hundreds of researchers in Australia and around the world working together to bring advanced genomics into standard health care.

After training as a child neurologist, I became increasingly fascinated by genetics and its potential to predict, diagnose and help treat disease. The lure of research drew me back to the lab, with a major focus on inherited muscle diseases like muscular dystrophy, which can lead to lifelong disability in affected children and adults. My work in this area led me to discover the effects of the gene ACTN3, which influences muscle power and recovery from damage and was subsequently dubbed the gene for speed.

We studied elite athletes and demonstrated that ACTN3 is a major determinant of skeletal muscle performance, but my team has also recently shown that variations in ACTN3 influence disease severity and progression in Duchenne muscular dystrophy. We are now studying how it influences muscle-wasting associated with ageing, steroid use and cancer.

My research is just one example of how genomic medicine can make a tremendous difference. This led me to help establish Australian Genomics, a national network of clinical and laboratory genetics services, hospitals, universities, research institutions and patient advocacy groups working together to establish procedures to enable all Australians access to genomic health care. The Murdoch Childrens Research Institute is now at the forefront of the genomics revolution, translating the latest discoveries into clinical practice.

An accurate diagnosis is hugely important because it gives answers to both the patient and the clinician. In my work as a paediatrician, Ive seen parents desperately seeking an answer to the cause of their kids intellectual or physical disability, wanting to know about their childs future and whether they would have other affected children.

Previously, we just couldnt answer these questions. Advances in genetic technology mean all genes can now be sequenced quickly and cheaply, and the information used to predict, diagnose and treat rare diseases as well as many forms of cancer.

Medical genetics and genomics has changed dramatically since the mid 90s. In the past we were able to give families with affected children a clinical description, but couldnt accurately put a label on what exactly was wrong.

The Human Genome Project and the development and rollout of advanced next-generation, ultrarapid gene sequencing have been an absolute game changer. I couldnt have imagined that wed be using genome technologies in the clinic within two years of using it in a research setting, increasing the diagnostic rate fivefold, and having geneticists working side by side with intensive care physicians to provide that diagnosis within three days.

We can now provide a genetic diagnosis for 50 to 90% of our families and answer these difficult questions.

Genomics is absolutely going to transform healthcare delivery. Using global data gathered and shared responsibly from millions of people, we can be much more accurate in making a prediction about the individual. We will be able to move to a healthcare model of prediction, prevention, early intervention and targeted treatment, and eventually improve and maintain the wellness of the population rather than focusing solely on illness.

This will no doubt come with significant challenges. To overcome these we need to approach genomics at the local and national level, and partner globally to be able to apply our insights to individuals accurately and with meaning.

Its incredibly important we engage at a public level so the community can understand our work. We need to bring the public along on this journey and explain the applications and great benefits of applying big data and genomic technologies to benefit individual patients. Its up to us as doctors and researchers to convey those messages accurately, strongly and with a united voice.

Research Australias Health and Medical Research Awards are important because they increase the visibility of science in general and medical research in particular within the community. They bring recognition to the researchers behind some of Australias most exciting medical and health discoveries, and kickstart conversations we need to be having to harness the possibilities of science for community benefit.

See the rest here:
In Conversation with Professor Kathryn North - Australian Hospital + Healthcare Bulletin

FILE PHOTO: The company's logo is seen at a building of Swiss drugmaker Novartis in Rotkreuz, Switzerland, January 29, 2020. REUTERS/Arnd Wiegmann

ZURICH (Reuters) - Swiss drugmaker Novartis on Friday won a key European recommendation for its gene therapy Zolgensma against spinal muscular atrophy (SMA), clearing a hurdle for $2.1 million per patient treatment for approval in Europe within months.

The European Medicines Agencys (EMA) Committee for Human Medicines (CHMP) recommended conditional approval for Zolgensma for certain patients: those with Type 1 SMA, the severest form of the disease, or for SMA patients with up to three copies of the so-called SMN2 gene, an indicator of the diseases severity.

The EMAs conditional approval is meant to speed up access to medicines for unmet needs, based on less-complete data than normally expected.

Typically the European Commission approves medicines for use shortly after a CHMP recommendation, and Novartis is expecting a decision by June. The medicine, the worlds costliest one-time treatment at its U.S. list price, has already been approved in the United States and Japan.

Novartis is counting on the gene therapy becoming a billion-dollar-per-year seller. Zolgensma is the second treatment for SMA to be approved after Biogens Spinraza three years ago. Roche is expecting its oral drug risdiplam to win U.S. regulators blessing in May.

Reporting by John Miller; Editing by Michael Shields

More:
Novartis wins key European recommendation for gene therapy Zolgensma - Reuters

The "Beijing Expert Consensus Statement on the Standardized Application of Next-Generation Sequencing Technology in Clinical Tests - Tumor (1st Edition)" has been officially published in Chinese Medical Journal. The drafting of this statement was led by Beijing Center for Clinical Laboratory, Beijing Society of Laboratory Medicine, Capital Medical University-Clinical Laboratory Diagnostics Department, and Beijing Quality Control and Improvement Center for Medical Laboratory Tests. It represents the first authoritative consensus on the standardized application of next-generation sequencing (NGS) technology in oncological clinical practice within China. It consequently serves as a base for standardized operation and management of NGS clinical laboratories. Genetron Holdings Limited ("Genetron Health") has been highly recognized by the drafting agencies, and ranks first place in the acknowledgements for its outstanding contribution.

NGS testing enables detection of somatic mutation in solid tumors; this statement elaborates on its intended clinical use, testing method establishment and optimization, LDTs analytical validation, and key pre-, in- and post-analysis quality assurance steps. Such testing is currently used to provide guidance for tumor targeted medicine and monitoring, as well as to evaluate immunotherapy efficacy. With the emergence of biomarkers, new NGS technology continues to be introduced to clinical testing, and the uses of technology are expected to expand further. The consensus statement will be amended accordingly to adapt to the guidelines for NGS-based tumor gene mutation detection in clinical practice.

Genetron Health is committed to providing quality products and services. The company actively work with institutions, experts and peers to promote the regularized and standardized application of NGS technology, and promote the development of precision medicine to benefit more patients.

About Genetron Health

Genetron Health is a leading and fast-growing precision oncology company in China that aims to provide one-stop genomic profiling solutions for multiple scenarios covering early screening, diagnosis and monitoring, and biopharmaceutical services. The company collaborates with over 400 hospitals and dozens of biopharmaceutical companies and research institutions and has developed a large proprietary genomic database.

Genetron Health has established R&D centers in both the United States and China, two manufacturing facilities with both ISO 13485:2016 certification and ISO 9001:2015 certification in China and five clinical laboratories in Beijing (CLIA accreditation and CAP certification), Shanghai, Hangzhou, Chongqing and Guangzhou. The R&D capacities of Genetron Health are supported by a best-in-class research and development team led by scientists at the forefront of cancer genomics research. The company has published many research papers in highly influential worldwide peer-reviewed scientific journals, such as Nature Genetics, Nature Communications, Cell Research and PNAS.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200320005341/en/

Contacts

For media inquiries, please contact:Huairan LiuE-mail: pr@genetronhealth.com

Excerpt from:
Genetron Health Contributes to Chinas First Expert Consensus Statement on the Standardized Clinical Application of NGS Testing for Oncology - Yahoo...

Mar 12th 2020

THE ATOMIC bomb convinced politicians that physics, though not readily comprehensible, was important, and that physicists should be given free rein. In the post-war years, particle accelerators grew from the size of squash courts to the size of cities, particle detectors from the scale of the table top to that of the family home. Many scientists in other disciplines looked askance at the money devoted to this big science and the vast, impersonal collaborations that it brought into being. Some looked on in envy. Some made plans.

The idea that sequencing the whole human genome might provide biology with some big science of its own first began to take root in the 1980s. In 1990 the Human Genome Project was officially launched, quickly growing into a global endeavour. Like other fields of big science it developed what one of the programmes leaders, the late John Sulston, called a tradition of hyperbole. The genome was Everest; it was the Apollo programme; it was the ultimate answer to that Delphic injunction, know thyself. And it was also, in prospect, a cornucopia of new knowledge, new understanding and new therapies.

By the time the completion of a (rather scrappy) draft sequence was announced at the White House in 2000, even the politicians were drinking the Kool-Aid. Tony Blair said it was the greatest breakthrough since antibiotics. Bill Clinton said it would revolutionise the diagnosis, prevention and treatment of most, if not all, human diseases. In coming years, doctors increasingly will be able to cure diseases like Alzheimers, Parkinsons, diabetes and cancer by attacking their genetic roots.

Such hype was always going to be hard to live up to, and for a long time the genome project failed comprehensively, prompting a certain Schadenfreude among those who had wanted biology kept small. The role of genetics in the assessment of peoples medical futures continued to be largely limited to testing for specific defects, such as the BRCA1 and BRCA2 mutations which, in the early 1990s, had been found to be responsible for some of the breast cancers that run in families.

To understand the lengthy gap between the promise and the reality of genomics, it is important to get a sense of what a genome really is. Although sequencing is related to an older technique of genetic analysis called mapping, it produces something much more appropriate to the White House kitchens than to the Map Room: a recipe. The genes strung out along the genomes chromosomesbig molecules of DNA, carefully packedare descriptions of lifes key ingredients: proteins. Between the genes proper are instructions as to how those ingredients should be used.

If every gene came in only one version, then that first human genome would have been a perfect recipe for a person. But genes come in many varietiesjust as chilies, or olive oils, or tinned anchovies do. Some genetic changes which are simple misprints in the ingredients specification are bad in and of themselvesjust as a meal prepared with fuel oil instead of olive oil would be inedible. Others are problematic only in the context of how the whole dish is put together.

The most notorious of the genes with obvious impacts on health were already known before the genome was sequenced. Thus there were already tests for cystic fibrosis and Huntingtons disease. The role of genes in common diseases turned out to be a lot more involved than many had naively assumed. This made genomics harder to turn into useful insight.

Take diabetes. In 2006 Francis Collins, then head of genome research at Americas National Institutes of Health, argued that there were more genes involved in diabetes than people thought. Medicine then recognised three such genes. Dr Collins thought there might be 12. Today the number of genes with known associations to type-2 diabetes stands at 94. Some of these genes have variants that increase a persons risk of the disease, others have variants that lower that risk. Most have roles in various other processes. None, on its own, amounts to a huge amount of risk. Taken together, though, they can be quite predictivewhich is why there is now an over-the-counter genetic test that measures peoples chances of developing the condition.

In the past few years, confidence in sciences ability to detect and quantify such genome-wide patterns of susceptibility has increased to the extent that they are being used as the basis for something known as a polygenic risk score (PRS). These are quite unlike the genetic tests people are used to. Those single-gene tests have a lot of predictive value: a person who has the Huntingtons gene will get Huntingtons; women with a dangerous BRCA1 mutation have an almost-two-in-three chance of breast cancer (unless they opt for a pre-emptive mastectomy). But the damaging variations they reveal are rare. The vast majority of the women who get breast cancer do not have BRCA mutations. Looking for the rare dangerous defects will reveal nothing about the other, subtler but still possibly relevant genetic traits those women do have.

Polygenic risk scores can be applied to everyone. They tell anyone how much more or less likely they are, on average, to develop a genetically linked condition. A recently developed PRS for a specific form of breast cancer looks at 313 different ways that genomes vary; those with the highest scores are four times more likely to develop the cancer than the average. In 2018 researchers developed a PRS for coronary heart disease that could identify about one in 12 people as being at significantly greater risk of a heart attack because of their genes.

Some argue that these scores are now reliable enough to bring into the clinic, something that would make it possible to target screening, smoking cessation, behavioural support and medications. However, hope that knowing their risk scores might drive people towards healthier lifestyles has not, so far, been validated by research; indeed, so far things look disappointing in that respect.

Assigning a PRS does not require sequencing a subjects whole genome. One just needs to look for a set of specific little markers in it, called SNPs. Over 70,000 such markers have now been associated with diseases in one way or another. But if sequencing someones genome is not necessary in order to inspect their SNPs, understanding what the SNPs are saying in the first place requires that a lot of people be sequenced. Turning patterns discovered in the SNPs into the basis of risk scores requires yet more, because you need to see the variations in a wide range of people representative of the genetic diversity of the population as a whole. At the moment people of white European heritage are often over-represented in samples.

The first genome cost, by some estimates, $3bn

The need for masses of genetic information from many, many human genomes is one of the main reasons why genomic medicine has taken off rather slowly. Over the course of the Human Genome Project, and for the years that followed, the cost of sequencing a genome fell quicklyas quickly as the fall in the cost of computing power expressed through Moores law. But it was falling from a great height: the first genome cost, by some estimates, $3bn. The gap between getting cheaper quickly and being cheap enough to sequence lots of genomes looked enormous.

In the late 2000s, though, fundamentally new types of sequencing technology became available and costs dropped suddenly (see chart). As a result, the amount of data that big genome centres could produce grew dramatically. Consider John Sulstons home base, the Wellcome Sanger Institute outside Cambridge, England. It provided more sequence data to the Human Genome Project than any other laboratory; at the time of its 20th anniversary, in 2012, it had produced, all told, almost 1m gigabytesone petabyteof genome data. By 2019, it was producing that same amount every 35 days. Nor is such speed the preserve of big-data factories. It is now possible to produce billions of letters of sequence in an hour or two using a device that could easily be mistaken for a chunky thumb drive, and which plugs into a laptop in the same way. A sequence as long as a human genome is a few hours work.

As a result, thousands, then tens of thousands and then hundreds of thousands of genomes were sequenced in labs around the world. In 2012 David Cameron, the British prime minister, created Genomics England, a firm owned by the government, and tasked initially with sequencing 100,000 genomes and integrating sequencing, analysis and reporting into the National Health Service. By the end of 2018 it had finished the 100,000th genome. It is now aiming to sequence five million. Chinas 100,000 genome effort started in 2017. The following year saw large-scale projects in Australia, America and Turkey. Dubai has said it will sequence all of its three million residents. Regeneron, a pharma firm, is working with Geisinger, a health-care provider, to analyse the genomes of 250,000 American patients. An international syndicate of investors from America, China, Ireland and Singapore is backing a 365m ($405m) project to sequence about 10% of the Irish population in search of disease genes.

Genes are not everything. Controls on their expressionepigentics, in the jargonand the effects of the environment need to be considered, too; the kitchen can have a distinctive effect on the way a recipe turns out. That is why biobanks are being funded by governments in Britain, America, China, Finland, Canada, Austria and Qatar. Their stores of frozen tissue samples, all carefully matched to clinical information about the person they came from, allow study both by sequencing and by other techniques. Researchers are keen to know what factors complicate the lines science draws from genes to clinical events.

Today various companies will sequence a genome commercially for $600-$700. Sequencing firms such as Illumina, Oxford Nanopore and Chinas BGI are competing to bring the cost down to $100. In the meantime, consumer-genomics firms will currently search out potentially interesting SNPs for between $100 and $200. Send off for a home-testing kit from 23andMe, which has been in business since 2006, and you will get a colourful box with friendly letters on the front saying Welcome to You. Spit in a test tube, send it back to the company and you will get inferences as to your ancestry and an assessment of various health traits. The health report will give you information about your predisposition to diabetes, macular degeneration and various other ailments. Other companies offer similar services.

Plenty of doctors and health professionals are understandably sceptical. Beyond the fact that many gene-testing websites are downright scams that offer bogus testing for intelligence, sporting ability or wine preference, the medical profession feels that people are not well equipped to understand the results of such tests, or to deal with their consequences.

An embarrassing example was provided last year by Matt Hancock, Britains health minister. In an effort to highlight the advantages of genetic tests, he revealed that one had shown him to be at heightened risk of prostate cancer, leading him to get checked out by his doctor. The test had not been carried out by Britains world-class clinical genomics services but by a private company; critics argued that Mr Hancock had misinterpreted the results and consequently wasted his doctors time.

23andMe laid off 14% of its staff in January

He would not be the first. In one case, documented in America, third-party analysis of genomic data obtained through a website convinced a woman that her 12-year-old daughter had a rare genetic disease; the girl was subjected to a battery of tests, consultations with seven cardiologists, two gynaecologists and an ophthalmologist and six emergency hospital visits, despite no clinical signs of disease and a negative result from a genetic test done by a doctor.

At present, because of privacy concerns, the fortunes of these direct-to-consumer companies are not looking great. 23andMe laid off 14% of its staff in January; Veritas, which pioneered the cheap sequencing of customers whole genomes, stopped operating in America last year. But as health records become electronic, and health advice becomes more personalised, having validated PRS scores for diabetes or cardiovascular disease could become more useful. The Type 2 diabetes report which 23andMe recently launched looks at over 1,000 SNPs. It uses a PRS based on data from more than 2.5m customers who have opted to contribute to the firms research base.

As yet, there is no compelling reason for most individuals to have their genome sequenced. If genetic insights are required, those which can be gleaned from SNP-based tests are sufficient for most purposes. Eventually, though, the increasing number of useful genetic tests may well make genome sequencing worthwhile. If your sequence is on file, many tests become simple computer searches (though not all: tests looking at the wear and tear the genome suffers over the course of a lifetime, which is important in diseases like cancer, only make sense after the damage is done). If PRSs and similar tests come to be seen as valuable, having a digital copy of your genome at hand to run them on might make sense.

Some wonder whether the right time and place to do this is at birth. In developed countries it is routine to take a pinprick of blood from the heel of a newborn baby and test it for a variety of diseases so that, if necessary, treatment can start quickly. That includes tests for sickle-cell disease, cystic fibrosis, phenylketonuria (a condition in which the body cannot break down phenylalanine, an amino acid). Some hospitals in America have already started offering to sequence a newborns genome.

Sequencing could pick up hundreds, or thousands, of rare genetic conditions. Mark Caulfield, chief scientist at Genomics England, says that one in 260 live births could have a rare condition that would not be spotted now but could be detected with a whole-genome sequence. Some worry, though, that it would also send children and parents out of the hospital with a burden of knowledge they might be better off withoutespecially if they conclude, incorrectly, that genetic risks are fixed and predestined. If there is unavoidable suffering in your childs future do you want to know? Do you want to tell them? If a child has inherited a worrying genetic trait, should you see if you have it yourselfor if your partner has? The ultimate answer to the commandment know thyself may not always be a happy one.

This article appeared in the Technology Quarterly section of the print edition under the headline "Welcome to you"

Read this article:
Genomics took a long time to fulfil its promise - The Economist

Mar 12th 2020

NEENA NIZAR is 42 years old, a professor of business studies and just 122cm tall. The ends of her bones are soft and pliable: on an x-ray they look frayed, like old paintbrushes. During her childhood and adolescence in Dubai she was operated on 30 times. The source of her problem remained a mystery. In 2010, after three decades of wondering, she finally received a diagnosis: Jansens Metaphyseal Chondrodysplasia, a condition first recognised in the 1930s. Her problems stem from a broken copy of just one of her 20,000 genes.

Dr Nizar is in some ways very unusual. Fewer than one in 200m people have the mutation to the PTH1R gene that causes Jansens disease. In other ways she is like everyone else. Although few people have a defect as debilitating, everyones health, and ill-health, is tied to the contents of their genomes. All genomes contain arrangements of genes that make psychological disorders, cancers, dementias or circulatory diseases either more of a problem or less of one. Everyone has genes that make them better or worse at metabolising drugs, more or less likely to benefit from specific forms of exercise, better able to digest some foods than others.

The same arrangement will never be seen twice. Though for identical twins the differences are the height of subtlety, each of the 7.5bn human genomes sharing the planet is unique. That irreducible diversity represents a challenge to many of the 20th centurys greatest medical advances, which were based on a one-size-fits-all approach. Personalising medicine is an enticing opportunity for improvement.

Good doctors have always treated their patients as individuals. In the 20th century blood tests, X-rays, body scans and other diagnostic tools made the specifics of each patients particular problems ever more visible. A spectacular reduction in the cost of reading, or sequencing, the DNA bases that make up human genetic information is adding a new level of individuality. It is now possible to inspect genetic differences with an ease previously unimaginable, and thus to know something about propensities to disease well before any symptoms show up.

Nobody knows exactly how many human genomes have been fully sequenced, and different sequencing procedures read the genome to different degreesthere are quick skims and painstaking philological studies. But the number is in the millions (see chart). By the 2030s genome sequencing is likely to be as routine in some places as taking a pin-prick of blood from a babys heel is todayit may even be part of the same procedure. Genome science is becoming a matter of practical medicine. New therapies that make it possible to adjust or edit this genetic inheritance are coming to market.

This flood of data is allowing medicine to become more precise and more personalin many ways, the p-words are two sides of the same coin. Previously recognised genetic diseases, such as Jansens, have been traced to specific genes and can be connected to defects in the proteins they create (almost all genes describe proteins, and proteins do almost all the bodys chemical work). Most of these diseases are rare, in that they typically affect no more than one person in 2,000 in the general population. But with over 6,000 such rare diseases now recognised, this means they are common in the aggregate. In Britain one in 17 people can expect to suffer from a rare disease at some point.

Studies of genetic diseases are not just a worthwhile end in themselves. Understanding what goes wrong when a specific protein is out of whack can reveal basic information about the bodys workings that may be helpful for treating other ailments. And the growing understanding of how large sets of genes may contribute to disease is making it possible to pick out the patients most at risk from common diseases like diabetes, heart conditions and cancer. That will help doctors personalise their interventions. In theory, the rise in access to personal genetic information allows individuals to better calculate these risks and to take pre-emptive action. In practice, so far, few people seem to do so.

Genomics is not the only source of new personal-health data. Just as all genomes are unique, so are the lives that all those genome-carriers lead. The increase in other forms of data about individuals, whether in other molecular information from medical tests, electronic health records, or digital data recorded by cheap, ubiquitous sensors, makes what goes on in those lives ever easier to capture. The rise of artificial intelligence and cloud computing is making it possible to analyse this torrent of data.

Almost 4bn people carry smartphones that can monitor physical activity. It is estimated that by 2022, 1bn people may be wearing a device such as a smart watch that can monitor their heart rate. The data-driven giants and startups of Silicon Valley are eager to help. Consumers no longer need to go to a doctor for a genome scan or to engage with a wide range of opinion about what ails them, or will ail them. The pharmaceutical companies used to dominating medicine are working hard to keep up. So are doctors, hospitals and health systems.

These possibilities are not without their risks, drawbacks and potential for disappointment. The ability to pinpoint what has gone wrong in a genome does not make it easy to fix. Moreover, as technology helps people monitor themselves in more ways, the number of the worried well will swell and unnecessary care will grow. Many could be done real harm by an algorithmic mirage.

Beyond this, the move fast and break things attitude common in tech companies sits uneasily with first, do no harm. And the untrammelled, unsupervised and unaccountable means of data accrual seen in other industries which have undergone digital transformations sits uneasily with concerns over medical privacy.

The very nature of medicine, though, means that the future will not just be a matter of business goals, research cultures, technological prowess, wise practice and well-crafted regulations. It will also be subject to the driving interests of particular individuals in ways never seen before. The development of gene-based medical research in Britain was deeply affected by the short, difficult life of Ivan Cameron, whose father, David Cameron, did much to build up genomics when he was prime minister. Many of those working in this field are impelled by personal loss.

And then there are those whose interests stem from the way in which their own genes shape their lives. People like Dr Nizar, who is now crafting a new research agenda for Jansens disease. There may only be 30 people in the world who suffer from it. But two of them are her children, and they are in ceaseless pain. Science knows why; medicine cannot yet help. We believe in miracles, she says. She is also working to make one happen.

This article appeared in the Technology Quarterly section of the print edition under the headline "Populations of one"

See the rest here:
Medicine is getting to grips with individuality - The Economist

The excitement about cell and gene therapies is almost tangible within the biotech and pharma industry. Over 950 companies are actively developing advanced therapies, which are expected to make exceptional improvements to peoples lives in the next decade. Although hopes are high, the industry still faces a number of challenges in cell and gene therapy manufacturing, mainly around being able to deliver these often difficult to make, complex treatments at the scale needed to meet patient demand.

The unprecedented growth of the industry, alongside the need to develop scalable manufacturing strategies, has led to a number of challenges that need to be addressed urgently. Previously, patient numbers were so small that processes were highly manual and required numerous skilled operators. However, the recent success of early gene therapy trials means upscaling now needs to be considered right from the start.

In the early days the aim was just to get to the clinic, said Lindsey Clarke, Head of Cell and Gene Therapy EMEA at Bio-Techne. Scale didnt come into it so much, but now the conversations we are having focus much more on making these complex therapies at a scale needed for a commercial medicine. There are increased efforts on finding solutions that dont just work for trials with 10 patients, but will still work at 1000 times that scale.

Life science tools and technology provider, Bio-Techne, has made it its mission to further support the cell and gene therapy industry by channeling its expertise into developing technologies that can help to scale manufacturing processes. The companys commitment is highlighted by its recent investment into a new good manufacturing practice (GMP) manufacturing facility in St Paul, Minnesota, US, that will focus on producing raw materials for use in cell and gene therapy applications.

We have realized that if all our customers are to be successful with their therapies then there will be a huge demand for raw materials, Clarke explained. So weve started building that capability, ahead of time. But its not just about supply, we are also innovating, from simple things like looking closely at the format our products come in and making them more compatible with large-scale manufacturing to whole new product ranges.

Bio-Technes investment in the new GMP manufacturing facility is a solution to meet the growing demand for raw materials needed for cell and gene therapy manufacturing. But its just one piece of a large puzzle: cell and gene therapy developers also need to consider the complex logistics required to deliver their therapies to the clinic, particularly when its an autologous therapy.

The process from the patient to the clinician, to the apheresis collection, to the manufacturing site, then the complex manufacturing process and then delivery back to the patient is highly complex.

Another key challenge closely related to upscaling is the great risk of human error in manual processes. Many of the cell and gene manufacturing processes currently in place have been developed with small patient numbers in mind and involve manual steps.

Humans are an excellent source of variability and risk, explained Clarke. When youre manufacturing in a GMP environment, you need highly-skilled, trained operators and there is a shortage of them out there. Automation is going to be key to address this issue. Not only does it reduce the manpower that is required, but it can also streamline the processes and make them less risky, more scalable, and reproducible as well, Clarke added.

With cell and gene therapy products, various analytical methods are used to assess critical quality attributes during development and manufacturing. These reflect the identity, potency, purity, safety, and stability of the product. However, such methods are frequently complex, non-standardized, time-consuming, and performed manually by trained operators.

Organizations such as Cell and Gene Therapy Catapult have called for the development of new analytical solutions for quality testing of advanced therapies throughout the manufacturing process. More automated analytical technologies have the potential to increase facility throughput and make quality control (QC) faster, less error-prone, more reproducible, and more GMP compliant.

Although Bio-Techne has a long-standing history of developing quality proteins, antibodies, small molecules, and immunoassays, it has expanded into automated protein analytical technologies in recent years.

For viral and non-viral vectors, Bio-Technes ProteinSimple branded platforms are rapidly being adopted by cell and gene therapy developers for assessment of vector identity, purity, and stability. Compared to traditional methods like Western blot, SDS-PAGE, and ELISA, ProteinSimples technology platform is based on capillary electrophoresis and microfluidics and provides a fully automated and accurate quantitative analysis of vectors.

We are also seeing Micro-Flow Imaging (MFI), a more common image-based analytical platform in biologics, used to characterize subvisible particles for quality control of cell and gene therapy products, explained Kamar Johnson, Commercial Development Manager in Cell and Gene Therapy at Bio-Techne. These robust automated platforms offer ease of use, rapid time to result, and software that meets GMP requirements.

Collaboration lies at the heart of successful innovation. It is especially important at the interface between process development and manufacturing, said Johnson.

Not everyone is an expert in everything, we all have our particular niches of expertise, added Clarke. We believe that we need to collaborate to get the innovation that will help change the way we manufacture cell and gene therapies. Collaboration is the key to solving the challenges of the cell and gene therapy industry.

On that note, Bio-Techne recently partnered with Fresenius Kabi and Wilson Wolf to form a new joint venture that provides manufacturing technologies and processes for the development and commercialization of new cell and gene therapies.

The collaboration combines Bio-Technes expertise of proteins, reagents, media, and gene editing technologies with Fresenius Kabis Lovo cell processing system and the bioreactor expertise from Wilson Wolf with its G-Rex technology that is designed as a scalable platform for personalized cell therapies.

As processes develop and technologies evolve, the cell and gene therapy space will be confronted with new challenges. At Bio-Techne, the team is keeping an eye out for interesting trends that might affect the industry.

I see the induced pluripotent stem cell (iPSC) therapy field continuing to grow with more allogeneic cell therapies being developed, says Johnson. Allogeneic manufacturing is potentially less complicated than autologous manufacturing due to the ability to provide off-the-shelf products when patients need them.

Although the challenges in cell and gene therapy manufacturing remain a problem, companies like Bio-Techne are establishing quicker, simpler, and more automated options within quality control, manufacturing, and process development.

Wherever we go, we see newer technologies supporting cell and gene therapy manufacturing, says Clarke. Within our industry, changes come so rapidly and the treatments have shown so much promise that there is a lot of focus on cell and gene therapies. This puts a lot of pressure on us as an industry to provide these treatments. I believe that collaboration is the key to tackling this problem.

To learn more about the challenges in cell and gene therapy manufacturing and how to solve them, visit Bio-Technes website or get in touch with the experts here!

Images via Shutterstock.com

Author: Larissa Warneck

Excerpt from:
Tackling the Challenges in Cell and Gene Therapy... - Labiotech.eu