Category Archives: Gene Medicine

PENNINGTON, N.J. and SAN DIEGO, Jan. 8, 2021 /PRNewswire/ -- OncoSec Medical Incorporated (NASDAQ:ONCS) (the "Company" or "OncoSec") today announced the first patient was dosed in OMS-104, an investigator-initiated Phase 2 trial evaluating TAVO (tavokinogene telseplasmid), the Company's intratumoral DNA plasmid-based interleukin-12 (IL-12) therapy administered using its gene delivery platform (gene electrotransfer), in combination with the anti-PD-1 checkpoint inhibitor OPDIVO (nivolumab) as a neoadjuvant therapy prior to surgery in patients with operable, locally or regionally advanced melanoma. The trial is designed to evaluate if the addition of TAVO can improve clinical outcomes already observed when using nivolumab alone as a neoadjuvant therapy.

Anti-PD1 checkpoint inhibitors, when administered as a neoadjuvant therapy, have shown encouraging clinical results, but rapid recurrence remains an issue for many patients. TAVO in combination with OPDIVO may drive deep anti-tumor immune responses and complete elimination of tumors prior to surgery, leading to improved long-term clinical outcomes for a significant proportion of treated patients. TAVO in combination with another anti-PD-1 checkpoint inhibitor, KEYTRUDA (pembrolizumab), has already been shown to enhance overall response rate and partial tumor responses in patients with anti-PD-1 checkpoint-refractory metastatic melanoma in OncoSec's KEYNOTE-695 registration directed Phase 2 clinical trial.

"While studies have shown relapse and overall survival advantages when checkpoint inhibitors are given alone following surgery, there is a need to investigate novel immunotherapeutic agents such as TAVO that can be given preoperatively in order to further enhance the clinical efficacy of immunotherapy in patients with advanced melanoma," said Armad A. Tarhini, M.D., Ph.D., Leader of the OMS-104 trial and Senior Member and Professor at the H. Lee Moffitt Cancer Center and Research Institute and the University of South Florida Morsani College of Medicine. "The neoadjuvant approach utilizing TAVO in combination with checkpoint inhibitors as being tested in this study may improve operability, pathologic tumor response and long-term disease control, which is highly desirable for these patients, who continue to have a high risk of recurrence and progression despite the use of standard therapy after surgery."

OMS-104 (NCT04526730) is a Phase 2 open-label, single arm study investigating intratumoral TAVO delivered by gene electrotransfer, or short electric pulses, plus nivolumab as neoadjuvant therapy in patients with operable locally-regionally advanced melanoma. The trial aims to enroll 33 patients and consists of three phases:

1) Neoadjuvant phase, where TAVO will be administered intratumorally using gene electrotransfer in three cycles on days one and eight every four weeks and nivolumab will be administered after TAVO on day eight of each cycle via 30-minute intravenous (IV) infusion;

2) Surgical phase consisting of a definitive surgery that will be scheduled 2-4 weeks after the last dose of nivolumab following radiologic and clinical assessment; and

3) Adjuvant phase, where nivolumab monotherapy will begin 2-4 weeks after surgery and will be administered for up to nine four-week cycles.

The primary endpoint is pathological complete response, estimated based on the proportion of participants with no viable tumor on histologic assessment at definitive surgery after the 12-week neoadjuvant period.

Daniel J. O'Connor, President and Chief Executive Officer of OncoSec, added, "TAVO delivers DNA plasmid-based IL-12 directly into the tumor using gene electrotransfer, which demonstrably enhances the immunogenicity of the treated tumors to yield productive 'in situ' vaccines. This principle has yielded striking results in post-PD-1 patients and is likely relevant in this earlier clinical setting. We look forward to exploring the utility of TAVO as a potential neoadjuvant therapy in a variety of solid tumor settings for patients in need of more effective treatment options."

About TAVOOncoSec's gene delivery technology combines TAVO(tavokinogene telseplasmid), a DNA plasmid-based interleukin-12 (IL-12), with an intra-tumoral gene delivery platform (gene electrotransfer) to achieve endogenous IL-12 production in the tumor microenvironment that enables the immune system to target and attack tumors throughout the body. TAVO has demonstrated a local and systemic anti-tumor response in several clinical trials, including the pivotal Phase 2b trial KEYNOTE-695 for metastatic melanoma and the KEYNOTE-890 Phase 2 trial in triple negative breast cancer (TNBC). TAVO has received both Orphan Drug and Fast-Track Designation by the U.S. Food & Drug Administration for the treatment of metastatic melanoma.

About OncoSec Medical IncorporatedOncoSec Medical Incorporated (the "Company," "OncoSec," "we" or "our") is a late-stage biotechnology company focused on developing cytokine-based intratumoral immunotherapies to stimulate the body's immune system to target and attack cancer. OncoSec's lead immunotherapy investigational product candidate TAVO (tavokinogene telseplasmid) enables the intratumoral delivery of DNA-based interleukin-12 (IL-12), a naturally occurring protein with immune-stimulating functions. The technology, which employs geneelectrotransfer, is designed to produce a controlled, localized expression of IL-12 in the tumor microenvironment, enabling the immune system to target and attack tumors throughout the body. OncoSec has built a deep and diverse clinical pipeline utilizing TAVO as a potential treatment for multiple cancer indications either as a monotherapy or in combination with leading checkpoint inhibitors; with the latter potentially enabling OncoSec to address a great unmet medical need in oncology: anti-PD-1 non-responders. Results from recently completed clinical studies of TAVO have demonstrated a local immune response, and subsequently, a systemic effect as either a monotherapy or combination treatment approach along with an acceptable safety profile, warranting further development. In addition to TAVO, OncoSec is identifying and developing new DNA-encoded therapeutic candidates and tumor indications for use with its new Visceral Lesion Applicator (VLA), to target deep visceral lesions, such as liver, lung or pancreatic lesions. For more information, please visitwww.oncosec.com.

TAVO is a trademark of OncoSec Medical Incorporated.

KEYTRUDAis a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

OPDIVO is a registered trademark of Bristol-Myers Squibb Company.

Risk Factors and Forward-Looking StatementsThis release, as well as other information provided from time to time by the Company or its employees, may contain forward-looking statements that involve a number of risks and uncertainties that could cause actual results to differ materially from those anticipated in the forward-looking statements. Forward-looking statements provide the Company's current beliefs, expectations and intentions regarding future events and involve risks, uncertainties (some of which are beyond the Company's control) and assumptions. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. You can identify forward-looking statements by the fact that they do not relate strictly to historical or current facts. These statements may include words such as "anticipate," "believe," "could," "estimate," "expect," "intend," "may," "plan," "potential," "should," "will" and "would" and similar expressions (including the negative of these terms). Although we believe that expectations reflected in the forward- looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. The Company intends these forward-looking statements to speak only at the time they are published on or as otherwise specified and does not undertake to update or revise these statements as more information becomes available, except as required under federal securities laws and the rules and regulations of the Securities Exchange Commission ("SEC"). In particular, you should be aware that the success and timing of our clinical trials, including safety and efficacy of our product candidates, patient accrual, unexpected or expected safety events, the impact of COVID-19 on the supply of our candidates or the initiation or completion of clinical trials and the usability of data generated from our trials may differ and may not meet our estimated timelines. Please refer to the risk factors and other cautionary statements provided in the Company's Annual Report on Form 10-K for the fiscal year ended July 31, 2020 and subsequent periodic and current reports filed with the SEC (each of which can be found at the SEC's website http://www.sec.gov), as well as other factors described from time to time in the Company's filings with the SEC.

Company ContactKim Jaffe, Ph.D.Assistant Vice President, Business Development & Operations+1-858-210-7330 [emailprotected]

Media ContactPatrick Bursey LifeSci Communications+1-646-970-4688[emailprotected]

SOURCE OncoSec Medical Incorporated

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OncoSec Announces First Patient Dosed in Phase 2 Trial of TAVO Plus OPDIVO as Neoadjuvant Therapy for Melanoma - PRNewswire

SAN FRANCISCO, Jan. 11, 2021 (GLOBE NEWSWIRE) -- Vineti, developer of the leading digital platform of record for personalized therapeutics, today announced a new suite of flexibility features for its Personalized Therapy Management (PTM) solution. These new PTM capabilities deliver unprecedented real-time process controls for advanced therapy manufacturers and Healthcare Providers, ultimately providing better care for patients.

Advanced therapies, such as CAR-T cell therapies, are produced via the most complex supply chain in the history of medicine, with rigorous regulatory requirements every step of the way. Manufacturing batches are typically small often just one single patient-specific product per batch and rely on highly variable manufacturing processes driven by multiple stakeholders scattered across different geographies and facilities. Orchestrating the production, transport, and patient delivery of each batch requires a high degree of flexibility, so that manufacturers can make adjustments and troubleshoot challenges in real time. Keeping each patient product moving quickly, safely, and compliantly demands digital solutions.

As the leader in advanced therapy supply chain orchestration technology, Vineti knows first-hand what types of support these transformative therapies require. Vinetis new set of PTM flexibility features solves critical supply chain workflow challenges that could otherwise hinder advanced therapies and keep some patients including those facing cancer or rare genetic disorders from receiving the personalized treatments they need.

We know what it takes to deliver advanced therapies at scale, and our PTM platform is making that happen through continuous updates and improvements, said Vineti CEO and Co-founder Amy DuRoss. This new set of flexibility-related features is just one of many ways well be expanding our platform, enabling standards and industrial scale for advanced therapies, and helping to provide better patient care throughout the year ahead.

PTM Label Printing

The new PTM Label Printing solution enables flexible in-process labeling for advanced therapies. Accurate, up-to-date patient and product information, on each and every label, is essential for patient safety. But the in-process nature of the label also has the potential to introduce a great deal of complexity and risk of error. An advanced therapy in-process labeling system requires flexibility, so that advanced therapy manufacturers can control what label content gets printed where and by whom, while maintaining rigorous compliance and quality.

Vinetis new PTM Label Printing solution provides multiple options for label printing, even on a per-site basis, ranging from printing to existing on-site printers or cloud connected printers. The flexibility of the PTM labeling solution enables Vineti to support a wide range of label printing use cases. The system supports a wide variety of label content types and standards, including ISBT-128 and SEC, to provide top-tier compliance and privacy protections.

Order Status Tracking and Rescheduling

The updated PTM Order Status Tracking solution enables an end-to-end view of each patient product journey, while providing even more real-time flexibility and control. A wide range of biopharmaceutical teams supporting an advanced therapy, from manufacturing and supply chain management to market access and commercialization, can use PTMs Order Status Tracking to monitor and respond to key processes for the ordering, collection, manufacturing, transportation, and infusion of each patient product.

Order Status Tracking enables manufacturers to check the progress of each order to see if critical steps are complete, delayed, or on time. The solution also now enables rescheduling, one of the most frequent challenges in advanced therapies. Key steps can now be rescheduled via the Order Status Tracking feature set, and those changes can then be cascaded through the rest of the patient journey to keep all milestones updated and tightly coordinated. The end result is more simplicity and greater control for each patient-specific process.

Additional product information

Learn more about PTM Label Printing.View a short demo of PTM Order Status Tracking and Rescheduling.Learn more about the PTM Platform solution.

About Vinetis PTM PlatformThe Vineti Personalized Therapy Management (PTM) platform is the essential engine for advanced therapy supply chains. This industry-leading, purpose-built cloud service is trusted by biopharma clients worldwide to industrialize and scale advanced therapies, ensuring standards, patient safety, security, compliance, and a seamless customer experience. The PTM platform replaces outdated, costly, disparate, bespoke systems with a single enterprise-grade foundation for scaling personalized therapeutics worldwide. Solving the challenges of medicines most complex supply chain at every stage of clinical development and beyond, PTM accelerates access to advanced therapies and helps biopharmaceutical manufacturers transform patients lives.

About VinetiVineti is the first commercial, configurable cloud-based platform to expand patient access to life-saving cell and gene therapies. Vineti was co-founded by GE and the Mayo Clinic to solve the key challenges that patients, medical providers, biopharmaceutical companies, and regulators face in the delivery and commercialization of individualized therapies. Now a fully independent company, Vineti offers a digital platform of record to integrate logistics, manufacturing, and clinical data for personalized therapies. The Vineti Personalized Therapy Management (PTM) platform aligns and orchestrates the cell and gene therapy process and improves product performance overall. The Vineti platform supports the full continuum of patient-specific therapies, including cancer vaccines and autologous and allogeneic cell therapies. Vineti is currently serving patients, healthcare providers, and researchers in hundreds of leading medical centers and manufacturing centers world-wide, on behalf of a growing number of biopharmaceutical partners. In 2019, the World Economic Forum honored Vineti as a World Economic Forum Technology Pioneer. Vineti is headquartered in San Francisco, California, with offices in Bethesda, Maryland and Yerevan, Armenia. For more information, please visit http://vineti.com.

Media ContactsVinetiStacy Henrypress@vineti.com

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Introducing new Vineti PTM flexibility features: next-gen label printing and rescheduling innovations deliver critical workflow options that advanced...

Carlos Julio Aponte, MD, still remembers his ankylosing spondylitis (AS) patient No. 1. The man, a former traffic controller, was referred to Aponte more than 4 decades ago, racked by such agonizing back pain since age 20 that he couldnt hold a job. No one could pinpoint the source of the mans mysterious ailment. One doctor suspected that the patients symptoms were all in his head and prescribed medication for that.

Aponte, a rheumatologist in Cleveland, asked his new patient when his back pain was the worst. In the morning, he replied. In fact, it took the man almost 2 hours to get out of bed and on his feet.

I said, Oh my god, you have ankylosing spondylitis! Aponte recalls.

Doctors today understand much more about inflammatory diseases like AS than they did in the 1970s. But even then, Aponte knew that morning stiffness that lasts more than an hour could be a telltale sign of AS.

The most common complaint with AS is back pain, something almost all of us have at one point or another. But the disease, a type of arthritis that mainly affects the spine, is very rare; out of 1,000 Americans, just two to five people may have it.

Despite recent medical advances, studies suggest the time from the start of AS symptoms to an accurate diagnosis still spans an average of 7-10 years. For one thing, the damage in the sacroiliac joints, which link your pelvis and low back, shows up on X-rays only in the later stages

AS also shows up differently in different people, says David Borenstein, MD, a rheumatologist and clinical professor of medicine at the George Washington University Medical Center. Whats more, there is no single, definitive diagnostic test for AS. So detecting the disease, Borenstein says, is not unlike rooting around for a needle in the haystack.

By Don Markhams count, it took him about 7 years to confirm that AS was responsible for his serious eye inflammation called uveitis. But when the 47-year-old Dallas native looks back, he thinks the correct answer actually may be closer to 30 years.

Markham remembers his mother strapping soothing hot towels on his knees when he was 10. The flares of pain would come and go. But those childhood episodes were mostly dismissed as growing pains. And they didnt deter Markham from growing up playing football and lifting weights.

But around the time Markham turned 40, his life took a scary turn when he got uveitis, a possible complication of AS that affects the eyes.

I basically couldnt see. I could make out shapes, but I was very light-sensitive, he says. The best way to describe it is its like almost being blind, but youre not blind.

The scare lasted about 6 weeks. Markhams eye doctors couldnt figure out the cause but guessed that it could be some kind of autoimmune disease. Without clear answers, Markham once again chose to blow it off.

Several years later, Markham thought he had twisted his left knee while kayaking. His doctor noticed that his inflammation markers were off the charts. But once again, the doctors remained baffled. One thought he might have cancer. Another suggested the reason for the pain and spreading inflammation might be neurological.

I dont know how many diagnoses they tried to come up with, and none of them was correct, Markham says. He struggled with the effects from his multiplying medications, including hallucinations. At one point, I was almost kind of suicidal.

After consulting nearly three dozen doctors -- but not until a fateful visit to a rheumatologist in Dallas -- Markham finally learned he had AS.

After one look at Markham and his medical history, the rheumatologist said, I already know what you have, but I need to do a test to confirm it.

Right away, Markham quit some of his medications and was weaned off others while he started on therapies to help with his AS. His recovery was rapid. He was back to lifting light weights in a few weeks and competing professionally in about a year.

Today, Markhams AS has progressed to the point that his spine is slightly fused. He regrets the time he wasted on incorrect diagnoses.

The problem is because it all depends on referrals to specialists, he says. But if a general practitioner has never seen AS, how would they know to refer you to a rheumatologist?

Some people with AS may have symptoms that can come from other conditions. They include pain in the buttocks and heels, psoriasis, and gut problems that can look like Crohns disease or ulcerative colitis.

Aponte, the rheumatologist, says many medical appointments are too rushed and unfocused to ferret out unusual diseases like AS.

Fifteen minutes with your patients is just not enough, Aponte says, adding that good communication is critical, especially for rheumatologists. I did find a lot of pearls asking the right questions, he says.

Borenstein, of George Washington University Medical Center, says doctors have gotten much better at identifying the signs of AS and the types of people who can get the disease. AS typically affects older teens and young adults, an age when theyre supposed to be at their peak health. Treatments have improved, too.

People don't need to suffer anywhere near the amount of trouble they've had in the past, he says.

AS once was thought to be almost exclusively a male disease. That, Borenstein says, led many doctors to overlook the symptoms in women. According to the latest estimates, women and girls account for about a quarter of AS cases. When it comes to a related condition called non-radiographic axial spondyloarthritis (nr-axSpA), the gender breakdown is evenly split.

Charis Ann Hill, a 33-year-old from Sacramento, CA, was raised as a girl by their mother in North Carolina but goes by the pronoun they. Their father, who Hill says wasnt involved in their life, had AS.

I knew he had a disease that I couldn't pronounce the name of, Hill says. But I knew that it wasn't going to happen to me because it was a man's disease.

Some 80%-95% of people with AS carry a gene called human leukocyte antigen B27 (HLA-B27). Children can inherit this gene from their parents. But you can get AS without carrying the gene. And the majority of people who have HLA-B27 dont get AS.

Hill, a model, was an athletic kid who ran and played soccer. When Hill hit their teens, the pain around their knees and other joints started. But Hill dismissed the symptoms as sports-related aches.

By the time Hill moved to California for college, their body started deteriorating.

One doctor brushed off Hills intense low back spasms as sports-related, again. At the time, Hill thought that made sense.

Hill consulted another doctor, who suggested they had anxiety and wrote a prescription. But Hill was unconvinced. They thought their symptoms were similar to ones their father had. So, they reached out to their estranged parent. In February 2013, their father emailed back and advised them to seek medical care specifically for AS.

Hill was officially diagnosed the next month.

I think a lot of people have relief when they finally know what's going on, Hill says. But they had the opposite reaction.

Hill saw their father once a year while growing up, and the memories of how the disease took a toll on his body brought on fear.

Immediately, I thought that's what my life is going to be, Hill says. Im going to become my dad.

It took time for Hill to come to terms with their lifelong condition. The long and frustrating quest to find a diagnosis was mentally and emotionally exhausting.

Depression and chronic disease are like cousins, they hang out a lot, Hill says.

On the flip side, Hill is grateful that their belated diagnosis allowed them to live care-free. It allowed them to have the time to indulge in adventures like bungee jumping, to play college soccer, and even to study abroad.

I went through 5 years of having what I was going through, and thats how long it took for me to accept it, Hill says. So don't let people pressure you into accepting something before you're ready.

SOURCES:

Carlos Julio Aponte, MD, board-certified rheumatologist and American College of Rheumatology member.

David Borenstein, MD, clinical professor of medicine, George Washington University Medical Center; partner, Arthritis and Rheumatism Associates, Washington, DC; executive editor, spinecommunity.com.

UpToDate: Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults, Pathogenesis of spondyloarthritis.

National Health Service (U.K.): Ankylosing spondylitis.

Spondylitis Association of America: Diagnosis of Ankylosing Spondylitis.

Johns Hopkins Arthritis Center: Ankylosing Spondylitis.

Current Rheumatology Reports: Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky.

Stanford Healthcare: How is Ankylosing Spondylitis diagnosed?

Excerpt from:
Why It Takes So Long to Diagnose Ankylosing Spondylitis - WebMD

"Being the first company to receive market authorization for such a broad, sequencing-based platform is a major milestone for Helix and for the genomics industry," said Dr. James Lu, M.D., Ph.D., co-founder and President of Helix. "Our research has shown that many people are at risk for highly actionable genetic conditions that could be prevented with better access to genetic screening. This first-of-its-kind market authorization will greatly accelerate adoption of genomic medicine that can personalize and improve the care that patients receive."

"This is a very important milestone and highlights the growing role of genomics in clinical care," said Francis deSouza, Illumina's President and Chief Executive Officer. "We congratulate Helix on this authorization, which moves us another step closer to ensuring people have access to genomic insights that can transform their lives."

"This tremendous collaboration with the FDA has allowed Helix to innovate a first-of-its-kind whole exome sequencing platform that will have a measurable impact on the ability to clear new genomic applications," said Marc Stapley, Chief Executive Officer of Helix. "We are excited to have pioneered this new regulatory authorization pathway to help health systems, life sciences companies, and payers to accelerate the advancement of genomic discoveries from bench to bedside."

Learn more at helix.com/FDA.

About the Helix Laboratory Platform & theHelix Genetic Health Risk App

The Helix Laboratory Platform is a qualitative in vitro diagnostic device intended for exome sequencing and detection of single nucleotide variants (SNVs) and small insertions and deletions (indels) in human genomic DNA extracted from saliva samples collected with OrageneDx OGD-610. The Helix Laboratory Platform is only intended for use with other devices that are germline assays authorized by FDA for use with this device. The device is performed at the Helix laboratory in San Diego, CA.

TheHelix Genetic Health Risk App uses qualitative genotypingto detect clinically relevant variants in genomic DNA isolated from human saliva collected from individuals 18 years with OrageneDx OGD-610 for the purpose of reporting and interpreting Genetic Health Risks (GHR): The Helix Genetic Health Risk App (HRA) for late-onset Alzheimer's disease is indicated for reporting of the e2/e2, e2/e3, e3/e3, e2/e4, e3/e4 and e4/e4 genotypes in the APOE gene. The report describes if a person's genetic result is associated with an increased or decreased risk of developing late-onset Alzheimer's disease. The e2 and e4 variants included in this report are found and have been studied in many ethnicities. Detailed risk estimates have been studied the most in people of European descent. The Helix Genetic Health Risk App (HRA) is to be used with the Helix Laboratory Platform.

About Helix

Helix is the leading population genomics company operating at the intersection of clinical care, research, and genomics. Its end-to-end platform enables health systems, life sciences companies, and payers to advance genomic research and accelerate the integration of genomic data into clinical care. Powered by one of the world's largest CLIA / CAP next-generation sequencing labs and the first and only FDA authorized whole exome sequencing platform, Helix supports all aspects of population genomics including recruitment and engagement, clinically actionable disease screening, return of results, and basic and translational research. In response to the COVID-19 public health crisis, Helix has launched a sensitive and scalable end-to-end COVID-19 test system to meet the needs of health systems, employers, governments, and other organizations across the country. Learn more at http://www.helix.com.

Media Contact Amy Fisher, Padilla for Helix [emailprotected] 612.805.5707

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Helix Laboratory Platform Granted the First and Only FDA Authorization for a Whole Exome Sequencing Platform - PRNewswire

News Release

Wednesday, January 6, 2021

Using a recently developed DNA base-editing technique, researchers correct accelerating aging disorder.

Researchers have successfully used a DNA-editing technique to extend the lifespan of micewith thegenetic variationassociated withprogeria, a rare genetic disease that causes extreme premature aging in children and can significantly shorten their life expectancy. The studywas published in the journalNature, and was a collaboration between the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health; Broad Institute of Harvard and MIT, Boston; and the Vanderbilt University Medical Center, Nashville, Tennessee.

DNA is made up of four chemical bases A, C, G and T. Progeria, which is also known as Hutchinson-Gilford progeria syndrome, is caused by a mutation in the nuclear laminA(LMNA) gene in which one DNA base C is changed to a T. This change increases the production of the toxic protein progerin, which causes the rapid aging process.

Approximately 1 in 4 million children are diagnosed with progeria within the first two years of birth, and virtually all of these children develop health issues in childhood and adolescence that are normally associated with old age, including cardiovascular disease (heart attacks and strokes), hair loss, skeletal problems, subcutaneous fat loss and hardened skin.

For this study, researchers used a breakthrough DNA-editing technique calledbase editing, which substitutes a single DNA letter for another without damaging the DNA, to study how changing this mutation might affect progeria-like symptoms in mice.

"The toll of this devastating illness on affected children and their families cannot be overstated," said Francis S. Collins, M.D., Ph.D., a senior investigator in NHGRI's Medical Genomics and Metabolic Genetics Branch, NIH director and a corresponding author on the paper. "The fact that a single specific mutation causes the disease in nearly all affected children made us realize that we might have tools to fix the root cause. These tools could only be developed thanks to long-term investments in basic genomics research.

The study follows another recent milestone for progeria research, as theU.S. Food and Drug Administration approved the first treatment for progeriain November 2020, a drug called lonafarnib. The drug therapy provides some life extension, but it is not a cure. The DNA-editing method may provide an additional and even more dramatic treatment option in the future.

David Liu, Ph.D., and his lab at the Broad Institute developed the base-editing method in 2016, funded in part by NHGRI.

"CRISPR editing, while revolutionary, cannot yet make precise DNA changes in many kinds of cells," said Dr. Liu, a senior author on the paper. "The base-editing technique we've developed is like a find-and-replace function in a word processor. It is extremely efficient in converting one base pair to another, which we believed would be powerful in treating a disease like progeria.

To test the effectiveness of their base-editing method, the team initially collaborated with the Progeria Research Foundation to obtain connective tissue cells from progeria patients. The team used the base editor on theLMNAgene within the patients cells in a laboratory setting. The treatment fixed the mutation in 90% of the cells.

The Progeria Research Foundation was thrilled to collaborate on this seminal study with Dr. Collinss group at the NIH and Dr. Lius group at Broad Institute, said Leslie Gordon, M.D., Ph.D., a co-author andmedical director of The Progeria Research Foundation, which partially funded the study. These study results present an exciting new pathway for investigation into new treatments and the cure for children with progeria.

Following this success, the researchers tested the gene-editing technique by delivering a single intravenous injection of the DNA-editing mix into nearly a dozen mice with the progeria-causing mutation soon after birth. The gene editor successfully restored the normal DNA sequence of theLMNAgene in a significant percentage of cells in various organs, including the heart and aorta.

Many of the mice cell types still maintained the corrected DNA sequence six months after the treatment. In the aorta, the results were even better than expected, as the edited cells seemed to have replaced those that carried the progeria mutation and dropped out from early deterioration. Most dramatically, the treated mice's lifespan increased from seven months to almost 1.5 years. The average normal lifespan of the mice used in the study is two years.

As a physician-scientist, its incredibly exciting to think that an idea youve been working on in the laboratory might actually have therapeutic benefit, said Jonathan D. Brown, M.D., assistant professor of medicine in the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. Ultimately our goal will be to try to develop this for humans, but there are additional key questions that we need to first address in these model systems.

Funding for the study was supported in part by NHGRI, the NIH Common Fund, the National Institute of Allergy and Infectious Diseases, the National Institute of Biomedical Imaging and Engineering, the National Institute of General Medical Sciences, the National Heart, Lung and Blood Institute and the National Center for Advancing Translational Sciences.

The National Human Genome Research Institute (NHGRI) is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at: https://www.genome.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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DNA-editing method shows promise to treat mouse model of progeria - National Institutes of Health

Every drug, from morphine to ibuprofen, has a standard dose -- a sort of one-size-fits all recommendation. But a new study suggests that when it comes to drug doses, "one size fits all" rarely applies.

Stanford Medicine professor Russ Altman, MD, PhD, and a team of scientists found that almost everyone (99.5% of individuals) is likely to have an abnormal or "atypical" response to at least one therapeutic drug. This, at least, is the case for people in the United Kingdom, as the study's data came from the UK Biobank, a project that collects, studies and shares data.

The research found that nearly a quarter of the study's participants had been prescribed a drug for which they were predicted to have an atypical response, based on their genetic makeup. On average, participants were predicted to have an atypical response to 10 drugs.

"Ultimately, the hope is that we can show how pervasive drug response variability is and encourage more doctors to rethink the standard prescription protocols that are largely used today and use genetic testing to predict and adjust forthis variability," said Altman, who is an expert in pharmacogenetics, a field that studies the intersection of drugs and genetics.

An "atypical" drug response encompasses a lot of things; but generally speaking, it means a certain drug might not affect one person the way it does another.

For instance, someone who has an atypical metabolic response might process that drug more efficiently, strengthening its initial effects but decreasing its efficacy over time. On the flip side, it could mean that that person is unable to metabolize the drug at all, leaving them without therapeutic aid, or even with dangerous side effects.

These differences in response to a drug are partially due to our genetics. Specific proteins -- workhorse molecules in the body -- break down drugs in order for the body to benefit from the therapeutic. Those proteins are regulated by a specific group of genes. Natural variation in those genes leads to differences in how an individual's body reacts to a given drug molecule.

Altman and his team, including graduate students and first authors of the study Greg McInnes and Adam Lavertu, analyzed data from nearly 500,000 participants.

For 230,000 participants in the study, the team had primary care data going back about 30 years. That includes which drugs had been prescribed, the dose, and all of the patient's different diagnoses. The researchers also had access to detailed genetic information about each patient. They paid special attention to genetic variations in a group of genes that are known to influence the human drug response.

By comparing an individual's genetics against the variations known to exist in the group of drug-response-associated genes, the researchers could predict how any given patient might respond to a drug.

"Pharmacogenetics as a field has been around for a long time, but it hasn't really been adopted into clinical use," McInnes told me. "It's been growing in the last few years as more people realize the impact that it could have on personalized health. For a long time, it's been this overlooked aspect of genetics that I think is actually one of the most clinically actionable advances that has come out of human genetics."

What's more, he said, the wide variability in the human drug response applies to common therapeutics most everyone has encountered or is familiar with -- ibuprofen, codeine, statins and beta blockers among others.

Moving forward, Lavertu says that the goal is to expand drug-gene variant interaction analyses into more diverse populations. The data from the UK Biobank provided critical insight, but it was largely only representative of a British population, where the majority shares European ancestry. A next step for the researchers is to investigate the same genes in the Million Veteran Program, a government research program with a more diverse study population, that is examining how genes, lifestyle and military exposures affect health and illness.

"Our hope is that doing more of these studies will help us find new relationships between genetic variants and drug response, so that pharmacogenetics can benefit more people," Lavertu said.

Photo byMicha Parzuchowski

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Based on genes, nearly everyone is likely to have an atypical response to at least one drug - Scope

Databridgemarketresearch.com added a new study on Global Bioinformatics Market Research Review 2020 that has been just made available providing an extensive knowledge and perceptions of the industry. In order to build a through future prospect for the Bioinformatics Market, the current and historical data has been gathered, classified and analyzed. Major industry experts and analysts examining the Bioinformatics Market worldwide were interviewed to obtain the data validating through secondary research findings.

Bioinformatics Market is expected to reach USD 26.33 billion by 2026 from USD 7.76 billion in 2018, at a CAGR of 16.5% in the forecast period 2019 to 2026. The new market report contains data for historic years 2017, the base year of calculation is 2018 and the forecast period is 2019 to 2026

Few of the major competitors currently working in the bioinformatics market areThermo Fisher Scientific (US), Illumina Inc. (US), Agilent Technologies, Inc. (US), QIAGEN (Netherlands), BGI (China), Wuxi NextCODE (China), Eurofins Scientific (Luxembourg), Waters Corporation (US), Sophia Genetics (Switzerland), Partek (US), DNASTAR (US), Dassault Systmes (France), DNAnexus, Inc. (US), Genebio (Switzerland), ASEBIO (Spain), PerkinElmer Inc. (US), abm Inc.(Canada) a few among others.

Scope of the Bioinformatics Market

Bioinformatics market is segmented on the basis of countries into U.S., Canada, Mexico in North America, Brazil, Argentina, Rest of South America as a part of South America, Germany, France, U.K., Italy, Spain, Netherlands, Belgium, Russia, Turkey, Switzerland, Rest of Europe in Europe, China, Japan, India, Australia, Singapore, Thailand, Malaysia, South Korea, Indonesia, Philippines, Rest of Asia Pacific (APAC)as a part of Asia-Pacific (APAC), U.A.E, Egypt, Saudi Arabia, South Africa, Israel, Rest of Middle East and Africa (MEA) as a part of Middle East and Africa (MEA).

To know more about the studyhttps://www.databridgemarketresearch.com/reports/global-bioinformatics-market

Market Drivers

Market Restraints

New Bioinformatics Market Development

Key Developments in the Market:

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Global Bioinformatics Market Latest Innovative Solutions to Boost Global Growth, Overview 2021||Agilent Technologies, Inc. (US), QIAGEN (Netherlands),...

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced its new 5-year strategy Alnylam P5x25 focused on the Companys planned transition to a top-5 biotech (measured by market capitalization) in the next 5 years through: sustainable innovation yielding transformative medicines for rare and common diseases for patients around the world and delivery of exceptional financial performance. Alnylam P5x25 extends the Companys decade-long heritage of providing longer term, 5-year business strategy guidance, the most recent of which was known as Alnylam 2020. In addition, Alnylam today reported preliminary fourth quarter and full year 2020 global net product revenues for ONPATTRO and GIVLAARI and provided additional updates on the Companys commercial launches, including initial OXLUMO demand.

New 5-Year Strategy: P5x25Alnylam ended last year exceeding all metrics for its Alnylam 2020 strategy, with 4 marketed products (versus 3), 12 clinical programs (versus 10), 6 of which are in late-stage development (versus 4), across 4 strategic therapeutic areas (versus 3).

The Companys Alnylam P5x25 strategy is aimed at Alnylams transition to a top 5 biotech company, as measured by market capitalization, over the next 5 years.

Specifically, the Company intends to end 2025 with the following profile**:

We executed well on our Alnylam 2020 strategy, exceeding all pre-set metrics and transitioning into a global, multi-product commercial company with a robust clinical pipeline and an organic product engine delivering sustainable innovation, a profile that has rarely been achieved in biotech history. It was especially gratifying to cap 2020 with positive Phase 3 HELIOS-A results for vutrisiran, which is set to become our 5th RNAi therapeutic to reach the market, if approved, said John Maraganore, Ph.D., CEO of Alnylam Pharmaceuticals. We are now thrilled to launch our new chapter with Alnylam P5x25, which is aimed at Alnylams planned transition to a top 5 biotech in market capitalization based on a proven and high-yielding technology for disruptive medical innovation and a foundational track record of commercial execution. Indeed, with Alnylam P5x25, we expect to sustainably and organically create and commercialize transformative rare and common disease medicines benefiting hundreds of thousands of patients around the world while delivering strong financial performance and profitability, resulting in a leading biotech profile.

2020 Preliminary Commercial and Financial Performance*ONPATTRO (patisiran), a commercial-stage RNAi therapeutic targeting transthyretin (TTR) for the treatment of polyneuropathy in adult patients with hATTR amyloidosis.

GIVLAARI (givosiran), a commercial-stage RNAi therapeutic for the treatment of adults with acute hepatic porphyria (AHP).

OXLUMO (lumasiran), a commercial-stage RNAi therapeutic for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels in pediatric and adult patients.

Finally, the Company today reported that it expects its full year 2020 non-GAAP operating loss to be substantially improved relative to the prior year, marking 2019 as Alnylams peak non-GAAP operating loss year as the Company transitions towards a self-sustainable financial profile.

Further, at December 31, 2020, Alnylam had preliminary cash, cash equivalents, and marketable securities of approximately $1.9 billion, as compared to $1.5 billion at December 31, 2019. The Company balance sheet was strengthened by the 2020 strategic financing collaboration with Blackstone.

We are extremely pleased with ONPATTRO and GIVLAARI performance in the fourth quarter and cumulatively for the year, reflecting strong commercial execution, a substantial increase in demand and new patient adds, despite the ongoing COVID-19 pandemic. Additionally, were pleased to report that strong top-line revenue growth at the upper end of our guidance range and disciplined R&D and SG&A investments have delivered on a lower non-GAAP operating loss for 2020 compared with the prior year. We believe were now firmly on our way toward a self-sustainable financial profile with significant growth from four revenue generating assets and moderated operating expenses, and a balance sheet that supports achievement of profitability without the need to access the equity markets, said Jeff Poulton, Chief Financial Officer of Alnylam. As we now launch our Alnylam P5x25 strategy, were committed to delivering consistently strong financial performance driven by 40% or greater revenue CAGR over the next five years with non-GAAP profitability achieved within the period.

Alnylam management will discuss these preliminary selected financial results and commercial updates during a webcast presentation at the 39th Annual J.P. Morgan Healthcare Conference tomorrow, Monday, January 11, 2021, at 8:20 a.m. ET.

About RNAiRNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of todays medicines by potently silencing messenger RNA (mRNA) the genetic precursors that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam PharmaceuticalsAlnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylams commercial RNAi therapeutic products are ONPATTRO (patisiran), GIVLAARI (givosiran), and OXLUMO (lumasiran) and Leqvio (inclisiran) being developed and commercialized by Alnylams partner Novartis. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its Alnylam P5x25 strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit http://www.alnylam.com and engage with us on Twitter at @Alnylam or on LinkedIn.

Alnylam Forward Looking StatementsVarious statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam's views and plans with respect to its new 5-year Alnylam P5x25 strategy, its intentions to achieve the metrics associated with this strategy including to become a profitable, top 5 biotech company, its unaudited, preliminary selected financial results for 2020, the potential for RNAi therapeutics, including ONPATTRO, GIVLAARI, OXLUMO, Leqvio (inclisiran) and vutrisiran, its plans for the continuing launch of its commercial products and the advancement of vutrisiran through regulatory review and toward the market, the achievement of additional pipeline milestones, and the continued development and commercialization of Leqvio (inclisiran) by its partner, Novartis, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic, such as the scope and duration of the outbreak, government actions and restrictive measures implemented in response, the broad availability of safe and effective vaccine(s), material delays in diagnoses of rare diseases, initiation or continuation of treatment for diseases addressed by Alnylam products, or in patient enrollment in clinical trials, potential supply chain disruptions, and other potential impacts to Alnylams business, the effectiveness or timeliness of steps taken by Alnylam to mitigate the impact of the pandemic, and Alnylams ability to execute business continuity plans to address disruptions caused by the COVID-19 or any future pandemic; the finalization and audit of Alnylams fourth quarter and 2020 fiscal year financial results which could potentially result in changes or adjustments to the selected preliminary financial results presented herein; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all; actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing; delays, interruptions or failures in the manufacture and supply of its product candidates or its or its partner Novartis marketed products; obtaining, maintaining and protecting intellectual property; intellectual property matters including potential patent litigation relating to its platform, products or product candidates; obtaining regulatory approval for its product candidates, and maintaining regulatory approval and obtaining pricing and reimbursement for its products; successfully launching, marketing and selling its approved products globally; Alnylams ability to successfully expand the indication for ONPATTRO in the future; the ability of Novartis to successfully obtain and maintain additional regulatory approvals and pricing and reimbursement for Leqvio (inclisiran); competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's ability to manage its growth and operating expenses and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylams ability to establish and maintain strategic business alliances and new business initiatives; Alnylam's dependence on third parties, including Novartis, Regeneron and Vir, for the continued development and commercialization of certain products; the outcome of litigation; the risk of government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

* The preliminary selected financial results are unaudited, subject to adjustment, and provided as an approximation in advance of the Companys announcement of complete financial results in February 2021.**The Alnylam P5x25 metrics on Patients, Products, and Pipeline include proprietary and partnered products and programs.

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Alnylam Launches Alnylam P5x25 Strategy for Planned Transition to a Top Five Biotech in Market Capitalization Over Next Five Years - Business Wire

The lowest part of a childs brain is visible below the bottom of the skull in this MRI scan and shows evidence of a Chiari 1 malformation. Researchers at Washington University School of Medicine in St. Louis have shown that Chiari 1 malformation can be caused by variations in two genes linked to brain development, and that children with large heads are at increased risk of developing the condition. Credit: David Limbrick

Discovery could aid early screening, shed light on how Chiari malformation arises.

About one in 100 children has a common brain disorder called Chiari 1 malformation, but most of the time such children grow up normally and no one suspects a problem. But in about one in 10 of those children, the condition causes headaches, neck pain, hearing, vision and balance disturbances, or other neurological symptoms.

In some cases, the disorder may run in families, but scientists have understood little about the genetic alterations that contribute to the condition. In new research, scientists at Washington University School of Medicine in St. Louis have shown that Chiari 1 malformation can be caused by variations in two genes involved in brain development.

The condition occurs when the lowest parts of the brain are found below the base of the skull. The study also revealed that children with unusually large heads are four times more likely to be diagnosed with Chiari 1 malformation than their peers with normal head circumference.

The findings, published Dec. 21 in the American Journal of Human Genetics, could lead to new ways to identify people at risk of developing Chiari 1 malformation before the most serious symptoms arise. It also sheds light on the development of the common but poorly understood condition.

A lot of times people have recurrent headaches, but they dont realize a Chiari malformation is the cause of their headaches, said senior author Gabriel Haller, PhD, an assistant professor of neurosurgery, of neurology and of genetics. And even if they do, not everyone is willing to have brain surgery to fix it. We need better treatments, and the first step to better treatments is a better understanding of the underlying causes.

If people start experiencing severe symptoms like chronic headaches, pain, abnormal sensations or loss of sensation, or weakness, the malformation is treated with surgery to decompress the Chiari malformation.

Theres an increased risk for Chiari malformations within families, which suggests a genetic underpinning, but nobody had really identified a causal gene, Haller said. We were able to identify two causal genes, and we also discovered that people with Chiari have larger head circumference than expected. Its a significant factor, and easy to measure. If you have a child with an enlarged head, it might be worth checking with your pediatrician.

To identify genes that cause Chiari 1 malformation, Haller and colleagues sequenced all the genes of 668 people with the condition, as well as 232 of their relatives. Of these relatives, 76 also had Chiari 1 malformation and 156 were unaffected. The research team included first author Brooke Sadler, PhD, an instructor in pediatrics, and co-authors David D. Limbrick, Jr., MD, PhD, a professor of neurosurgery and director of the Division of Pediatric Neurosurgery, and Christina Gurnett, MD, PhD, a professor of neurologyand director of the Division of Pediatric and Developmental Neurology, among others.

Sequencing revealed that people with Chiari 1 malformation were significantly more likely to carry mutations in a family of genes known as chromodomain genes. Several of the mutations were de novo, meaning the mutation had occurred in the affected person during fetal development and was not present in his or her relatives. In particular, the chromodomain genes CHD3 and CHD8 included numerous variants associated with the malformation.

Further experiments in tiny, transparent zebrafish showed that the gene CHD8 is involved in regulating brain size. When the researchers inactivated one copy of the fishs chd8 gene, the animals developed unusually large brains, with no change in their overall body size.

Chromodomain genes help control access to long stretches of DNA, thereby regulating expression of whole sets of genes. Since appropriate gene expression is crucial for normal brain development, variations in chromodomain genes have been linked to neurodevelopmental conditions such as autism spectrum disorders, developmental delays, and unusually large or small heads.

Its not well known how chromodomain genes function since they have such a wide scope of activity and they are affecting so many things at once, Haller said. But they are very intriguing candidates for molecular studies, to understand how specific mutations lead to autism or developmental delay or, as in many of our Chiari patients, just to increased brain size without cognitive or intellectual symptoms. Wed like to figure out the effects of each of these mutations so that in the future, if we know a child has a specific mutation, well be able to predict whether that variant is going to have a harmful effect and what kind.

The association between chromodomain genes and head size inspired Haller and colleagues to measure the heads of children with Chiari malformations, comparing them to age-matched controls and to population averages provided by the Centers for Disease Control and Prevention. Children with Chiari tended to have larger than average heads. Those children with the largest heads bigger than 95% of children of the same age were four times more likely to be diagnosed with the malformation.

The findings suggest that children with larger heads or people with other neurodevelopmental disorders linked to chromodomain genes may benefit from screening for Chiari malformation.

A lot of kids that have autism or developmental disorders associated with chromodomain genes may have undiscovered Chiari malformations, Haller said. The only treatment right now is surgery. Discovering the condition early would allow us to watch, knowing the potential for serious symptoms is there, and perform that surgery as soon as its necessary.

Reference: Rare and de novo coding variants in chromodomain genes in Chiari I malformation by Brooke Sadler, Jackson Wilborn, Lilian Antunes, Timothy Kuensting, Andrew T. Hale, Stephen R. Gannon, Kevin McCall, Carlos Cruchaga, Matthew Harms, Norine Voisin, Alexandre Reymond, Gerarda Cappuccio, Nicola Burnetti-Pierri, Marco Tartaglia, Marcello Niceta, Chiara Leoni, Giuseppe Zampino, Allison Ashley-Koch, Aintzane Urbizu, Melanie E. Garrett, Karen Soldano, Alfons Macaya, Donald Conrad, Jennifer Strahle, Matthew B. Dobbs, Tychele N. Turner, Chevis N. Shannon, Douglas Brockmeyer, David D. Limbrick, Christina A. Gurnett and Gabe Haller, 21 December 2020, American Journal of Human Genetics.DOI: 10.1016/j.ajhg.2020.12.001

This study was funded by Sam and Betsy Reeves and the Park-Reeves Syringomyelia Research Consortium; the University of Missouri Spinal Cord Injury Research Program; the Childrens Discovery Institute of St. Louis Childrens Hospital and Washington University; the Washington University Institute of Clinical and Translational Sciences, grant number UL1TR000448 from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH); the Eunice Kennedy Shriver National Institute of Child Health & Human Development, award number U54HD087011 to the Intellectual and Developmental Disabilities Research Center at Washington University; the Swiss National Science Foundation, grant number 31003A_182632; and the Jrme Lejeune Foundation.

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Common Brain Malformation Affecting About 1 in 100 Children Traced to Its Genetic Roots - SciTechDaily

By Abbey Slattery, WRAL Digital Solutions

This article was written for our sponsor, the North Carolina Biotechnology Center.

Gene and cell therapies are paving the way to breakthrough treatments and potential cures for serious illnesses and diseases, from spinal muscular atrophy to Pompe Disease.

Pioneers scientists in this field call North Carolina home.

Research by Jude Samulski, Ph.D.,at the University of North Carolina at Chapel Hill used adeno-associated virus to deliver gene therapies. His findings created Bamboo Therapeutics, now part of Pfizer, and AskBio, acquired by Bayer. Charles Gersbach, Ph.D., leads Duke University's Center for Advanced Genomic Technologies, whose CRISPR research underpins a half-dozen startups. And North Carolina State University's Rodolphe Barrangou, Ph.D., uses a different CRISPR enzyme to edit genes. This technique underpins the work of Locus Biosciences.

With this foundation, North Carolina's strengths in biological manufacturing naturally created a cluster of gene and cell therapy manufacturing, including Novartis Gene Therapies, Audentes, an Astellas company, and more.

"Gene therapy alleviates the underlying cause of genetic diseases and acquired diseases. It aims to treat diseases by replacing, inactivating or introducing genes into cells either inside the body, or in vivo, or outside of the body, or ex vivo," said Jimmy Weirich, vice president and site head at Novartis Gene Therapies, a global healthcare company with a major manufacturing facility in Durham. "Each cell and gene therapy is designed based on detailed information about the roots of a patient's disease. Rather than treating symptoms, gene therapy works by repairing or enhancing cells at the genetic level."

According to Weirich, the aim of gene therapy is to halt a disease in its tracks or reverse its progress, as opposed to simply alleviating symptoms. The treatment is often only administered once.

At Novartis Gene Therapies, the company's goal is to develop and commercialize gene therapies for patients and families affected by rare and life-threatening neurological genetic diseases. Already, its initial gene therapy for spinal muscular atrophy has been approved in the U.S., Japan, the European Union, Israel, Brazil and Canada.

That treatment, the company's flagship gene therapy in neuroscience, Zolgensma, was approved in May 2019 in the U.S. to treat children less than two years old with SMA. Given as a one-time infusion, the treatment helps halt irreversible motor neuron loss and disease progression.

In developing this treatment, Novartis Gene Therapies hopes to change the lives of those afflicted with SMA.

"The healthcare industry in general and gene therapy in particular is incredibly fast-paced and changing every day. It's exciting and requires people who want to think differently about challenges and the solutions needed to be successful," said Weirich. "At the end of the day, though, it is all about our patients. To know that our hard work means we can change the life of one single patient and his or her family is an incredible feeling. There aren't many industries or jobs like that."

At Audentes, the company has a similar focus, utilizing gene therapies to target life-threatening and often rare diseases. Based in California with a location currently under construction in Sanford, Audentes develops gene therapies to treat conditions like X-Linked myotubular myopathy, Pompe disease, Duchenne muscular dystrophy and myotonic dystrophy.

The company is currently implementing its plans to construct a $109 million, state-of-the-art gene therapy manufacturing facility that employs 200. Growing its footprint in the Triangle brings further opportunities to the area, complementing the potential of gene therapies in general.

"One of the real benefits that we have when it comes to using DNA as the therapeutic agent is that it's incredibly flexible. It serves as the basic instructions that allow you to create antibodies, or enzymatic proteins, or RNA molecules with your gene therapy. You can take this very basic building block and design it in a way that allows it to interact and change just about any aspect of cellular biology and redirect and refocus it in a way that we think is beneficial to the patient," said Mathew Pletcher, Ph.D., senior vice president of research at Audentes.

"What gene therapy does is it takes a benign virus and gets rid of the viral elements that allow the virus to replicate and make multiple copies of itself. We get rid of that and then put in the DNA we wish to deliver into cells. So we hijack something that exists in nature and now use it as the vehicle to deliver therapeutic genes back into the patient's cells."

In the case of a condition like Duchenne muscular dystrophy, Audentes is able to use gene therapy to implement interventions like exon skipping a type of RNA splicing that redirects cells to skip over mutationa. Through these techniques, scientists can restore normal gene function by removing the mutation.

Locus Biosciences develops antibacterial products using CRISPR-enhanced bacteriophages. By targeting certain bacteria, this Morrisville biotech company employs precision therapy to treat bacterial diseases, disrupting the microbiomes of patients as little as possible.

"Historically, bacteriophages haven't been effective enough to fight serious infections because bacteria and bacteriophage co-evolved over billions of years into a sort of predator-prey relationship so they're in this sort of ecological balance. We addressed that by enhancing the killing capability of the bacteriophage using CRISPR," said Joseph Nixon, senior vice president of business development at Locus. "We add CRISPR-Cas3 instead of snipping the target DNA like a pair of scissors, it shreds it or chews it up like a Pac-Man. What we do is put the CRISPR-Cas3 constructs into the bacteriophage and thereby create a dual mechanism of action between the bacteriophage itself, killing some of the target bacterial cells and then CRISPR-Cas3 killing the rest."

In targeting treatment in such a way, Locus is able to make products that are significantly more effective than other bacteriophage products. The products it develops are used to target bacterial infections and microbiome diseases, including conditions like inflammatory bowel disease and colorectal cancer.

Audentes, Novartis Gene Therapies and Locus are helping to create gene and cell therapies that could change the lives of millions of people across the world and address diseases in ways that weren't previously possible. In addition to the medicines and treatments the companies provide, other companies are using similar methods to treat conditions like congenital blindness, cancer, diabetes, metabolic disorders and more.

"Audentes really is one of the pioneers charting this new course and an innovative approach that we think could really transform the entire landscape of medicine how we deliver it and the impact that it can make," said Pletcher. "Ultimately, we're at the beginning of a really exciting transformation in medicine that is going to make a real difference in people's lives. By having a nucleus of companies like ours, growth in the area can become an avalanche, where we all continue to build on top of each other."

Added Nixon, "The Triangle has a much lower cost than other leading areas, like Boston and San Francisco. Those lower costs, especially for companies like Locus, where we're funded by investor dollars, enable us to achieve more for the same amount of money. And of course, the programs with the NCBiotech Center are critical in helping to grow and sustain the life science industry in the state."

As that avalanche of opportunity continues to gain momentum, companies like these need a qualified workforce. According to Weirich, the ideal candidate for the industry should have the proper training and education, but also curiosity and a passion for helping others.

"There is a wide range of jobs, and, more importantly, career options, available within this industry. No matter the role of the job, it is fundamental for all of our employees to know that the work they do on a daily basis has a direct impact on our ability to produce life-saving therapies for our patients, and in the case of Zolgensma, our employees are literally saving the lives of newborn babies," said Weirich. "Most importantly, we are looking for people who feel as passionate as we do about the mission to make a difference in the lives of individuals and families faced with the challenge of rare diseases."

Photo Courtesy of Novartis

This article was written for our sponsor, the North Carolina Biotechnology Center.

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Producing the newest medicines - and potentially cures: gene and cell therapies - WRAL.com