Daily Archives: November 17, 2021

Introduction

The cells of a human being or other organism have parts called genes that control the chemical reactions in the cell that make it grow and function and ultimately determine the growth and function of the organism. An organism inherits some genes from each parent and thus the parents pass on certain traits to their offspring.

Gene therapy and genetic engineering are two closely related technologies that involve altering the genetic material of organisms.The distinction between the two is based on purpose.Gene therapy seeks to alter genes to correct genetic defects and thus prevent or cure genetic diseases.Genetic engineering aims to modify the genes to enhance the capabilities of the organism beyond what is normal.

Ethical controversy surrounds possible use of the both of these technologies in plants, nonhuman animals, and humans. Particularly with genetic engineering, for instance, one wonders whether it would be proper to tinker with human genes to make people able to outperform the greatest Olympic athletes or much smarter than Einstein.

If genetic engineering is meant in a very broad sense to include any intentional genetic alteration, then it includes gene therapy. Thus one hears of therapeutic genetic engineering (gene therapy) and negative genetic engineering (gene therapy), in contrast with enhancement genetic engineering and positive genetic engineering (what we call simply genetic engineering).

We use the phrase genetic engineering more narrowly for the kind of alteration that aims at enhancement rather than therapy. We use the term gene therapy for efforts to bring people up to normalcy and genetic engineering or enhancement genetic engineering for efforts to enhancement peoples capabilities beyond normalcy.

Two fundamental kinds of cell are somatic cells and reproductive cells. Most of the cells in our bodies are somatic cells that make up organs like skin, liver, heart, lungs, etc., and these cells vary from one another. Changing the genetic material in these cells is not passed along to a persons offspring. Reproductive cells are sperm cells, egg cells, and cells from very early embryos. Changes in the genetic make-up of reproductive cells would be passed along to the persons offspring. Those reproductive cell changes could result in different genetics in the offsprings somatic cells than otherwise would have occurred because the genetic makeup of somatic cells is directly linked to that of the germ cells from which they are derived.

Two problems must be confronted when changing genes. The first is what kind of change to make to the gene. The second is how to incorporate that change in all the other cells that are must be changed to achieve a desired effect.

There are several options for what kind of change to make to the gene. DNA in the gene could be replaced by other DNA from outside (called homologous replacement). Or the gene could be forced to mutate (change structure selective reverse mutation.) Or a gene could just be added. Or one could use a chemical to simply turn off a gene and prevent it from acting.

There are also several options for how to spread the genetic change to all the cells that need to be changed. If the altered cell is a reproductive cell, then a few such cells could be changed and the change would reach the other somatic cells as those somatic cells were created as the organism develops. But if the change were made to a somatic cell, changing all the other relevant somatic cells individually like the first would be impractical due to the sheer number of such cells. The cells of a major organ such as the heart or liver are too numerous to change one-by-one. Instead, to reach such somatic cells a common approach is to use a carrier, or vector, which is a molecule or organism. A virus, for example, could be used as a vector. The virus would be an innocuous one or changed so as not to cause disease. It would be injected with the genetic material and then as it reproduces and infects the target cells it would introduce the new genetic material. It would need to be a very specific virus that would infect heart cells, for instance, without infecting and changing all the other cells of the body. Fat particles and chemicals have also been used as vectors because they can penetrate the cell membrane and move into the cell nucleus with the new genetic material.

Gene therapy is often viewed as morally unobjectionable, though caution is urged. The main arguments in its favor are that it offers the potential to cure some diseases or disorders in those who have the problem and to prevent diseases in those whose genes predisposed them to those problems. If done on reproductive cells, gene therapy could keep children from carrying such genes (for unfavorable genetic diseases and disorders) that the children got from their patients.

Genetic engineering to enhance organisms has already been used extensively in agriculture, primarily in genetically modified (GM) crops (also known as GMO --genetically modified organisms). For example, crops and stock animals have been engineered so they are resistant to herbicides and pesticides, which means farmers can then use those chemicals to control weeds and insects on those crops without risking harming those plants. In the future genetic enhancement could be used to create crops with greater yields of nutritional value and selective breeding of farm stock, race horses, and show animals.

Genetically engineered bacteria and other microorganisms are currently used to produce human insulin, human growth hormone, a protein used in blood clotting, and other pharmaceuticals, and the number of such compounds could increase in the future.

Enhancing humans is still in the future, but the basic argument in favor of doing so is that it could make life better in significant ways by enhancing certain characteristics of people. We value intelligence, beauty, strength, endurance, and certain personality characteristics and behavioral tendencies, and if these traits were found to be due to a genetic component we could enhance people by giving them such features. Advocates of genetic engineering point out that many people try to improve themselves in these ways already by diet, exercise, education, cosmetics, and even plastic surgery. People try to do these things for themselves, and parents try to provide these things for their children. If exercising to improve strength, agility, and overall fitness is a worthwhile goal, and if someone is praised for pursuing education to increase their mental capabilities, then why would it not be worthwhile to accomplish this through genetics?

Advocates of genetic engineering also see enhancement as a matter of basic reproductive freedom. We already feel free to pick a mate partly on the basis of the possibility of providing desirable children. We think nothing is wrong with choosing a mate whom we hope might provide smart, attractive kids over some other mate who would provide less desirable children. Choosing a mate for the type of kids one might get is a matter of basic reproductive freedom and we have the freedom to pick the best genes we can for our children. Why, the argument goes, should we have less freedom to give our children the best genes we can through genetic enhancement?

Those who advocate making significant modification of humans through technology such as genetic engineering are sometimes called transhumanists.

Three arguments sometimes raised against gene therapy are that it is technically too dangerous, that it discriminates or invites discrimination against persons with disabilities, and that it may be becoming increasingly irrelevant in some cases.

The danger objection points out that a few recent attempts at gene therapy in clinical trials have made headlines because of the tragic deaths of some of the people participating in the trials. It is not fully known to what extent this was due to the gene therapy itself, as opposed to pre-existing conditions or improper research techniques, but in the light of such events some critics have called for a stop to gene therapy until more is known. We just do not know enough about how gene therapy works and what could go wrong. Specific worries are that

The discrimination objection is as follows. Some people who are physically, mentally, or emotionally impaired are so as the result of genetic factors they have inherited. Such impairment can result in disablement in our society. People with disabilities are often discriminated against by having fewer opportunities than other people. Be removing genetic disorders, and resulting impairment, it is true that gene therapy could contribute to removing one of the sources of discrimination and inequality in society. But the implicit assumption being made, the objection claims, is that people impaired through genetic factors need to be treated and made normal. The objection sees gene therapy as a form of discrimination against impaired people and persons with disabilities.

The irrelevance objection is that gene therapy on reproductive cells may in some cases already be superseded by in-vitro fertilization and selection of embryos. If a genetic disorder is such that can be detected in an early embryo, and not all embryos from the parent couple would have it, then have parents produce multiple embryos through in-vitro fertilization and implant only those free from the disorder. In such a case gene therapy would be unnecessary and irrelevant.

Ethicists have generally been even more concerned about possible problems with and implications of enhancement genetic engineering than they have been about gene therapy. First, there are worries similar to those about gene therapy that not enough is known and there may be unforeseen dangerous consequences. These worries may be even more serious given that the attempts are made not just toward normalcy but into strange new territory where humans have never gone before. We just do not know what freakish creatures might result from experiments gone awry.

Following are some other important objections:

Gene therapy is becoming a reality as you read this. Genetic engineering for enhancement is still a ways off. Plenty of debate is sure to occur over both issues.

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Gene Therapy and Genetic Engineering - MU School of Medicine

Genome editing allows scientists to alter the DNA in an organism, whether through adding, subtracting, or changing the genetic code at a specific location. There are many methods for editing DNA, but themost commonly mentioned are CRISPR-Cas9 and TALENs.

CRISPRs are repeated sequences of DNA interspersed with unique sequences of spacers. CRISPRs are naturally occurring, used by bacteria and archaea to fight off pathogens by slicing up the intruders genetic material and adding these slices to its own genome as a sort of library.

Since the pathogens genes become a part of the bacteriums genes, the bacteria can remember the pathogen and better fight it in the future.

Molecular biologists use CRISPR to study relationships between genes and how living things look and function. In medicine, this technology gives hope for creating new treatments to cure diseases that are currently incurable.

One way of using gene editing is to identify and deactivate genes that are causing diseases. That includes genes that increase the risk of a disease, or normal genes that, when mutated or dysfunctional, cause genetic diseases.

The immune system, however, can also interfere with gene editing and disturb treatment.

TALENs is another method being used for efficient gene editing. Xanthomonas genus bacteria wreak havoc on plants, injecting a protein called TAL that can shut down a plants genes. This protein might be bad for plants, but for scientists, its opened up the world of gene editing even more. TAL is made up of sections that can identify certain DNA nucleotides, and tinkering with these sections allows scientists to locate genes they want to edit.

Is CRISPR flawed?

A recent study has flagged a new safety signal that could potentially hurt the drug developers focused on CRISPRCas9 gene editing.

The condition known as chromothripsis has the potential to cause cancer eventually, according to the study conducted by St. Jude Childrens Research Hospital, the DanaFarber Cancer Institute, and Harvard Medical School.

When double-strand DNA breaks during CRISPR editing, there could be chromothripsis, a condition that results from the shattering of individual chromosomes and the haphazard rearrangement of genetic material subsequently.

According to an article published inNatureBiotechnology, none of the companies advancing the CRISPR-based therapies have considered the issue.

Is gene editing even ethical?

During the Olympics, the physiological prowess of elite athletes is clear, whether its the long-limbed volleyball players or the muscular weightlifters. Unsurprisingly, physiological advantages vary by sport, but theres a number of genetic advantages that can arise.

Lance Armstrong even without performance-enhancing drugs, still had a genetically powerful build for cycling: he has a higher maximum oxygen consumption than the average person and this is associated with genetics.

Michael Phelps, the most decorated Olympian of all time, naturally produceshalf the lactic acidof other Olympic swimmers. When we perform high-energy activities, the body switches from generating energy aerobically (with oxygen) to generating energy anaerobically (without oxygen). During this process, the body breaks down a substance called pyruvate into lactic acid. Thislactic acidtires out muscles, leaving them with that all-too-familiar burning sensation when you exercise. Since Phelps doesnt have as much lactic acid, hes able to recover from high-intensity activity quickly.

Could we create designer elite athletes using genome editing?

The US National Academy of Sciences and National Academy of Medicine have hosted an interdisciplinary committee to outline the regulatory standards and ethics of human gene modification. The very first of these regulations was that genome editing can occur if it is restricted topreventing the transmissionof a serious disease or condition.

The World Anti-Doping Agency recently placed gene editing on theirlist of prohibited practices and substances. Theres just one problem: Its extremely difficult to determine if someone has modified their genome.

In theory, we could genetically engineer children to grow into better athletes: a runner with stronger leg muscles, a taller volleyball or basketball player, an archer with pinpoint vision.

Moderna gets a jump on gene editing

Moderna has found a direction to volley their mountain of COVID-19 vaccine cash: gene editing.

Executives revealed during a second-quarter earnings call recently that Moderna is ready to expand its horizons with external technologies or products.

Modernas pulled in billions with its COVID-19 vaccine. The shot, which the company now aims to market as Spikevax, is expected to bring in about $20 billion this year, based on existing orders.

Moderna is interested in new opportunities in nucleic acid technologies, gene therapy, gene editing and mRNA, CEO Stphane Bancel said during the conference call.

Most likely, Moderna will start with hematopoietic stem cells, which is the companys bread-and-butter delivery method. Other companies working on gene editing include CRISPR Therapeutics, Precision Biosciences, Beam Therapeutics, and Sangamo Therapeutics.

Gene editing applications

The Global genome editing market is expected to reach $8.7 billion by 2026, according to Reportlinker.com.

Genome editing finds application in a large number of areas, such as mutation, therapeutics, and agriculture biotechnology. The rise in the number of chronic and infectious diseases is likely to expand the scope of genome editing in the coming years.

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Gene editing: Great for medicine but ethical issues arise

Discover how gene therapy can treat diseases caused by genetic mutations such as cystic fibrosis

Gene therapy seeks to repair genetic mutations through the introduction of healthy, working genes.

gene therapy, also called gene transfer therapy, introduction of a normal gene into an individuals genome in order to repair a mutation that causes a genetic disease. When a normal gene is inserted into the nucleus of a mutant cell, the gene most likely will integrate into a chromosomal site different from the defective allele; although that may repair the mutation, a new mutation may result if the normal gene integrates into another functional gene. If the normal gene replaces the mutant allele, there is a chance that the transformed cells will proliferate and produce enough normal gene product for the entire body to be restored to the undiseased phenotype.

Human gene therapy has been attempted on somatic (body) cells for diseases such as cystic fibrosis, adenosine deaminase deficiency, familial hypercholesterolemia, cancer, and severe combined immunodeficiency (SCID) syndrome. Somatic cells cured by gene therapy may reverse the symptoms of disease in the treated individual, but the modification is not passed on to the next generation. Germline gene therapy aims to place corrected cells inside the germ line (e.g., cells of the ovary or testis). If that is achieved, those cells will undergo meiosis and provide a normal gametic contribution to the next generation. Germline gene therapy has been achieved experimentally in animals but not in humans.

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cancer: Gene therapy

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Scientists have also explored the possibility of combining gene therapy with stem cell therapy. In a preliminary test of that approach, scientists collected skin cells from a patient with alpha-1 antitrypsin deficiency (an inherited disorder associated with certain types of lung and liver disease), reprogrammed the cells into stem cells, corrected the causative gene mutation, and then stimulated the cells to mature into liver cells. The reprogrammed, genetically corrected cells functioned normally.

Prerequisites for gene therapy include finding the best delivery system (often a virus, typically referred to as a viral vector) for the gene, demonstrating that the transferred gene can express itself in the host cell, and establishing that the procedure is safe. Few clinical trials of gene therapy in humans have satisfied all those conditions, often because the delivery system fails to reach cells or the genes are not expressed by cells. Improved gene therapy systems are being developed by using nanotechnology. A promising application of that research involves packaging genes into nanoparticles that are targeted to cancer cells, thereby killing cancer cells specifically and leaving healthy cells unharmed.

Some aspects of gene therapy, including genetic manipulation and selection, research on embryonic tissue, and experimentation on human subjects, have aroused ethical controversy and safety concerns. Some objections to gene therapy are based on the view that humans should not play God and interfere in the natural order. On the other hand, others have argued that genetic engineering may be justified where it is consistent with the purposes of God as creator. Some critics are particularly concerned about the safety of germline gene therapy, because any harm caused by such treatment could be passed to successive generations. Benefits, however, would also be passed on indefinitely. There also has been concern that the use of somatic gene therapy may affect germ cells.

Although the successful use of somatic gene therapy has been reported, clinical trials have revealed risks. In 1999 American teenager Jesse Gelsinger died after having taken part in a gene therapy trial. In 2000 researchers in France announced that they had successfully used gene therapy to treat infants who suffered from X-linked SCID (XSCID; an inherited disorder that affects males). The researchers treated 11 patients, two of whom later developed a leukemia-like illness. Those outcomes highlight the difficulties foreseen in the use of viral vectors in somatic gene therapy. Although the viruses that are used as vectors are disabled so that they cannot replicate, patients may suffer an immune response.

Another concern associated with gene therapy is that it represents a form of eugenics, which aims to improve future generations through the selection of desired traits. While some have argued that gene therapy is eugenic, others claim that it is a treatment that can be adopted to avoid disability. To others, such a view of gene therapy legitimates the so-called medical model of disability (in which disability is seen as an individual problem to be fixed with medicine) and raises peoples hopes for new treatments that may never materialize.

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gene therapy | Description, Uses, Examples, & Safety ...

Chroma Medicine thinks it can silence and activate genes via epigenetic editing, and the biotech uncovered itself with $125 million in financing to test the epigenome's potential in helping treat various diseases.

The biotech is working to create epigenetic editors that can turn on or turn off genesor perform a combination of the twoto regulate gene expression.

The epigenome is the system that informs cells how to comprehend DNA. Think of DNA as the hardware and the epigenome as the software that directs which genes are expressed and which are silenced, explained CEO Catherine Stehman-Breen, M.D., in an interview with Fierce Biotech.

Chroma's epigenetic editors are a "small tweak to the software package that sits on top of the hardware of the genome," said Vic Myer, Ph.D., president and chief scientific officer, in the joint interview. The "beauty of this system" is that Chroma's editor is only needed for a brief moment to change the local epigenetic mark set, he added.

This is done without nicks or cuts to the DNA itself, Stehman-Breen said.

RELATED:GV-backed Cambridge Epigenetix lines up $88M to roll out genetic sequencing technology

With the money in hand, Chroma will move the technology into in vivo proof-of-concept studies in mice and build out manufacturing capabilities, Myer said. The biotech has already reproduced the "critical experiments" conducted by the scientific founders, he added.

The executives declined to disclose which diseases or areas they'd tackle first. The funding will provide runway for a "couple of years," at which point Chroma will have the data to support the next round of financing, Stehman-Breen said.

The one-year-old startup has already combined forces with another biotech via its acquisition of Epsilen Bio, a Milan, Italy-based company working on a "somewhat parallel path,"Stehman-Breen said. Together, the companies are a "powerhouse in terms of epigenetic editing therapeutics," the CEO added.

Chroma's scientific co-founders include a team of epigenetic editing, gene editing and cell therapy experts, Stehman-Breen said. The groundwork was laid by Angelo Lombardo, Ph.D.,and Luigi Naldini, M.D., Ph.D., at the San Raffaele Telethon Institute for Gene Therapy. Chroma's other scientificoriginators include the University of California, San Francisco'sLuke Gilbert, Ph.D., Massachusetts General Hospital's Keith Joung, M.D., Ph.D., the Broad Institute's David Liu, Ph.D., and the Whitehead Institute's Jonathan Weissman, Ph.D.

For her part, Stehman-Breen'sresume includes stints as chief medical officer at Sarepta Therapeutics, chief R&D officer at Obsidian Therapeutics and vice president of global development at both Regeneron and Amgen. Prior to Chroma, Myer held interim C-suite roles at Korro Bio and Obsidian and was chief technology officer at gene-editing pioneer Editas Medicine from 2015 to 2019.

Atlas Venture and Newpath Partners provided seed capital for Chroma last year with Sofinnova Partners. Cormorant, Casdin Capital, Janus Henderson, Omega Funds, T. Rowe Price andWellington Management joined for the series A.

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Gene on, gene off: Chroma Medicine turns lights on with $125M to control gene expression with ex-Editas, Regeneron leaders - FierceBiotech

Gilmore ONeill, M.B., M.M.Sc., will depart the Company and serve in a consulting capacity through March 31, 2022

CAMBRIDGE, Mass., Nov. 17, 2021 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that, effective immediately, Louise Rodino-Klapac, Ph.D., executive vice president and chief scientific officer, has been named the Companys head of research and development (R&D) and will continue to serve in the role of chief scientific officer. Gilmore ONeill, M.B., M.M.Sc., who has served as head of R&D since 2018, will leave the Company at the end of November and remain in a consulting capacity until March 31, 2022.

Dr. Rodino-Klapac has been central to our efforts around the discovery and development of Sareptas gene therapy platform and was an early collaborator in the development of RNA-based therapies as a therapeutic option for patients with rare diseases, said Doug Ingram, president and chief executive officer, Sarepta. Her exceptional command of our core therapeutic platforms in RNA, gene therapy, and gene editing, and the strength of her scientific leadership has been and will be instrumental as Sarepta advances its industry-leading pipeline of genetic medicines.

Dr. Rodino-Klapac inherits a strong research and development function. Dr. ONeill led our research and development function during a period of enormous expansion and multiple successes, including approvals of our second and third RNA-based therapies for Duchenne muscular dystrophy, and the commencement of pivotal trials for our lead candidates in both our next-generation RNA platform and our gene therapy platform, added Mr. Ingram. On behalf of the entire team, I would like to thank Dr. ONeill for all of his contributions to Sarepta and to the patient communities we serve.

About Sarepta TherapeuticsSarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit http://www.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

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Forward-Looking StatementsThis press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding the potential benefits related to the announced leadership transition and Sareptas potential to advance its industry-leading pipeline of genetic medicines.

These forward-looking statements involve risks and uncertainties, many of which are beyond Sareptas control. Known risk factors include, among others: leadership transitions can be inherently difficult to manage and may cause uncertainty or a disruption to Sareptas business or may increase the likelihood of turnover in other key officers and employees; Sarepta may not be able to execute on its business plans and goals, including meeting its expected or planned regulatory milestones and timelines, clinical development plans, and bringing its product candidates to market, due to a variety of reasons, many of which may be outside of Sareptas control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover Sareptas product candidates and the COVID-19 pandemic; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2020, and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by Sarepta which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect the Companys business, results of operations and the trading price of Sareptas common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review the SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof, except as required by law.

Internet Posting of InformationWe routinely post information that may be important to investors in the 'For Investors' section of our website at http://www.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Investor Contact: Ian Estepan, 617-274-4052iestepan@sarepta.com

Media Contact: Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

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Sarepta Therapeutics Names Louise Rodino-Klapac, Ph.D., Head of Research and Development - Yahoo Finance

-Initiation of patient enrollment expected by year-end-

-Initiation of patient enrollment expected by year-end-

ZUG, Switzerland and CAMBRIDGE, Mass. and SAN DIEGO, Nov. 16, 2021 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (NASDAQ: CRSP), a biopharmaceutical company focused on developing transformative gene-based medicines for serious diseases, and ViaCyte, Inc., a clinical-stage regenerative medicine company developing novel cell replacement therapies to address diseases with significant unmet needs, today announced that Health Canada has approved the companies Clinical Trial Application (CTA) for VCTX210, an allogeneic, gene-edited, immune-evasive, stem cell-derived therapy for the treatment of type 1 diabetes (T1D). Initiation of patient enrollment is expected by year-end.

With the approval of our CTA, we are excited to bring a first-in-class CRISPR-edited cell therapy for the treatment of type 1 diabetes to the clinic, an important milestone in enabling a whole new class of gene-edited stem cell-derived medicines, said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. The combination of ViaCytes leading stem cell capabilities and CRISPR Therapeutics pre-eminent gene-editing platform has the potential to meaningfully impact the lives of patients living with type 1 diabetes.

Being first into the clinic with a gene-edited, immune-evasive cell therapy to treat patients with type 1 diabetes is breaking new ground as it sets a path to potentially broadening the treatable population by eliminating the need for immunosuppression with implanted cell therapies, said Michael Yang, President and Chief Executive Officer of ViaCyte. This approach builds on previous accomplishments by both companies and represents a major step forward for the field as we strive to provide a functional cure for this devastating disease.

The Phase 1 clinical trial of VCTX210 is designed to assess its safety, tolerability, and immune evasion in patients with T1D. This program is being advanced by CRISPR Therapeutics and ViaCyte as part of a strategic collaboration for the discovery, development, and commercialization of gene-edited stem cell therapies for the treatment of diabetes. VCTX210 is an allogeneic, gene-edited, stem cell-derived product developed by applying CRISPR Therapeutics gene-editing technology to ViaCytes proprietary stem cell capabilities and has the potential to enable a beta-cell replacement product that may deliver durable benefit to patients without requiring concurrent immune suppression.

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About CRISPR TherapeuticsCRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

About ViaCyteViaCyte is a privately held clinical-stage regenerative medicine company developing novel cell replacement therapies based on two major technological advances: cell replacement therapies derived from pluripotent stem cells and medical device systems for cell encapsulation and implantation. ViaCyte has the opportunity to use these technologies to address critical human diseases and disorders that can potentially be treated by replacing lost or malfunctioning cells or proteins. ViaCytes first product candidates are being developed as potential long-term treatments for patients with type 1 diabetes to achieve glucose control targets and reduce the risk of hypoglycemia and diabetes-related complications. To accelerate and expand ViaCytes efforts, it has established collaborative partnerships with leading companies, including CRISPR Therapeutics and W.L. Gore & Associates. ViaCyte is headquartered in San Diego, California. For more information, please visit http://www.viacyte.com and connect with ViaCyte on Twitter, Facebook, and LinkedIn.

CRISPR Therapeutics Forward-Looking StatementThis press release may contain a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements made by Dr. Kulkarni and Mr. Yang in this press release, as well as regarding CRISPR Therapeutics expectations about any or all of the following: (i) the safety, efficacy and clinical progress of our various clinical programs including our VCTX210 program; (ii) the status of clinical trials (including, without limitation, activities at clinical trial sites) and expectations regarding data from clinical trials; (iii) the data that will be generated by ongoing and planned clinical trials, and the ability to use that data for the design and initiation of further clinical trials; and (iv) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies, including as compared to other therapies. Without limiting the foregoing, the words believes, anticipates, plans, expects and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the potential for initial and preliminary data from any clinical trial and initial data from a limited number of patients not to be indicative of final trial results; the potential that clinical trial results may not be favorable; potential impacts due to the coronavirus pandemic, such as the timing and progress of clinical trials; that future competitive or other market factors may adversely affect the commercial potential for CRISPR Therapeutics product candidates; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics most recent annual report on Form 10-K, quarterly report on Form 10-Q and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at http://www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

CRISPR Therapeutics Investor Contact:Susan Kim+1-617-307-7503susan.kim@crisprtx.com

CRISPR Therapeutics Media Contact:Rachel Eides+1-617-315-4493rachel.eides@crisprtx.com

ViaCyte Investor Contact: David Carey, Lazar-FINN Partners+1-212-867-1768david.carey@finnpartners.com

ViaCyte Media Contact: Glenn Silver, Lazar-FINN Partners+1-973-818-8198glenn.silver@finnpartners.com

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CRISPR Therapeutics and ViaCyte, Inc. to Start Clinical Trial of the First Gene-Edited Cell Replacement Therapy for Treatment of Type 1 Diabetes -...

COVID-19 has been all-consuming. For nearly two years, the world has been focused on the race for vaccines, the pressures on providers, the best testing protocols, and simply staying safe.

COVID-19 also slowed some research efforts, but scientists still managed to seek solutions for many other pressing concerns Alzheimers disease, maternal mortality, and prostate cancer among them that have bedeviled patients for decades.

Below are eight medical advances that may not have grabbed your attention but could ultimately improve the lives of millions.

Assessing a stroke demands a rapid, life-or-death assessment: Is the culprit a clot, which requires a blood thinner, or bleeding in the brain, which requires surgery? Now, a portable MRI device can help make that assessment right at a patients bedside and in much less time than required by a trip to a standard machine.

The Swoop MRI which was created with input from Yale Medicine in New Haven, Connecticut received Food and Drug Administration (FDA) approval in August 2020 and is already at work in several U.S. hospitals.

The new portable machine offers many advantages over its massive cousin, says Yale neurologist Kevin Sheth, MD.

The very strong magnets in regular MRIs bring a lot of challenges, he explains. You need intensive power and cooling, precautions like a shielded room, and a lot of training. If you use a weaker magnet, all those problems go away.

The weaker magnet is effective, according to an August 2021 study, which asked clinicians to identify various cerebral pathologies using Swoop images. The goal is not to be as good as a high-magnet MRI, but to be good enough for clinical decisions, says Sheth, who co-authored the study but has no financial interest in Hyperfine, the Connecticut-based company that produces the machine.

Swoops size its smaller than some refrigerators eliminates the need to move frail patients down hospital hallways. Whats more, its cost around $100,000 compared to $1 million for the bigger machine puts it within reach of hospitals and regions with fewer resources. This could essentially democratize brain imaging, argues Sheth.

Prostate cancer strikes 1 out of 8 U.S. men, and it is expected to take more than 34,000 lives this year alone. When it metastasizes, the disease is almost always incurable, leaving physicians focused only on postponing death and improving patients lives.

A promising new approach has succeeded at both goals and did so among men with an advanced form of the disease whose condition had deteriorated despite receiving standard treatments.

In fact, it more than doubled how long patients lived without their cancer worsening, according to a paper published in September. The study, which followed 831 men in 10 countries for a median of 20 months, compared patients who continued to receive standard care with ones who got the new treatment.

The treatments name is complex: lutetium-177-PSMA-617. But its approach is straightforward: Drive radiation directly into a cancer cell while sparing healthy tissue around it.

The method uses a compound called PSMA-617 to hone in on a protein found almost exclusively in prostate cancer cells, explains Oliver Sartor, MD, study co-lead investigator and medical director of Tulane Cancer Center in New Orleans. Then, a radioactive particle carried by the compound blasts the cancer cells, wherever they are.

Its like a little smart bomb, says Sartor.

In September, the FDA granted the treatment priority review status, according to drug manufacturer Novartis, which funded the study. An answer is expected in the first half of 2022.

Sartor feels hopeful. Ive been working in prostate cancer for more than 30 years, and this is the largest advance Ive ever been associated with.

For more than 5,000 years, sickle cell disease (SCD) has caused untold suffering in people of African descent. In patients with the genetic illness, red blood cells are not round but crescent-shaped like a sickle and can clog blood vessels, depriving the body of oxygen and causing tremendous pain. For a long time, the only cure has been a bone marrow transplant, but new gene-editing techniques now may offer a safe and effective alternative.

In research conducted at Boston Childrens Hospital, scientists used a virus to switch off the gene that triggers cells sickling, according to a January 2021 study. The patients subsequently produced healthy red blood cells and nearly all were able to discontinue the blood transfusions SCD often requires.

One participant used to have transfusions every month but has not needed any in three years, says David Williams, MD, chief of the Division of Hematology/Oncology at Boston Childrens and head of the research team. This has completely changed his life.

The study followed six patients for a median of 18 months and found that the treatment completely halted the diseases more severe symptoms.

Im so happy for my sickle-cell patients. This is a terrible disease, notes Williams.

Next up for Williams is a trial with 25 patients. Meanwhile, SCD researchers elsewhere are studying other gene-editing techniques. All these approaches look promising, and we need a lot more research to determine if one or another is better, Williams says.

This is a very exciting time. In the past, we havent had any particularly good treatments, and now we have several possibilities," he adds.

When a womans uterus fails to contract after childbirth, tremendous blood loss can ensue, possibly leading to an emergency hysterectomy or even death. In fact, postpartum hemorrhage affects 3% to 10% of all childbirths in the United States and causes more than one-third of childbirth-related maternal deaths worldwide.

Treatment options include medications that dont always work and inserting a balloon to put pressure on the uterus much like exerting pressure on a cut that comes with risks and must remain in place for a day.

But providers now have another option.

A new vacuum device aids natural post-birth contractions, putting pressure on leaking blood vessels. The FDA approved the device the Jada vacuum uterine tamponade in September 2020 following a 12-site research study.

The vacuum approach is very logical since its like what the body is supposed to do, says Dena Goffman, MD, the primary investigator at Columbia University Irving Medical Center in Manhattan. Also, the vacuum is used for less time than the balloon roughly two or three hours. For moms, thats a big deal because it makes it easier to breastfeed, get out of bed, and bond with their child, she adds.

The vacuum controlled bleeding in a median of three minutes and successfully treated 94% of participants, according to the study, which was funded by the devices manufacturer, Alydia Health. In comparison, other research puts the balloons effectiveness at 87%.

When a patient has a postpartum hemorrhage and youre the doctor at the bedside, its scary because you know how quickly things can deteriorate, says Goffman. Using this device, when you see the bleeding slowing quickly and you can feel the uterus contracting, its just incredible.

Tearing an anterior cruciate ligament (ACL) the flexible band inside the knee that helps stabilize it can upend a sports career and sideline weekend athletes. Between 100,000 and 200,000 ACL tears occur each year in the United States.

The most effective repair option has been removing the ruptured ACL, harvesting a graft from the shin or elsewhere, sewing that tissue into the knee, and hoping both surgical sites heal well.

In December 2020, the FDA approved a simpler, more natural method: the Bridge-Enhanced ACL Repair (BEAR).

We basically stimulate the ACL to heal itself, says Martha Murray, MD, orthopedic surgeon-in-chief at Boston Childrens Hospital and BEARs creator.

The approach involves placing a protein-based sponge, prepared with some of the patients own blood, between the torn ACL ends. Murray explains that the blood promotes the connection of the two ACL pieces to the sponge and, ultimately, to each other.

So far, the approach has been tested on more than 100 patients. In a May 2020 study, patients and physicians reported that BEAR performed as well as the standard repair and without the graft surgery that can cause ongoing pain or weakness at the donor site. Miach Orthopaedics, which has the worldwide exclusive license for the BEAR implant, has already begun making it available through orthopedic surgeons in the United States.

For Murray, the experience has highlighted the value of serving as a physician-researcher. When youre faced with a patient with a problem and the current solution is imperfect, its great to be able to say, Were working on a better solution. Its incredibly gratifying.

For the first time since 2014, a new obesity medication has hit the market, offering hope to the 78 million Americans who face the many risks of excess weight: cancer, heart disease, diabetes, and complications from COVID-19, among others.

And the new medication semaglutide, also known as Wegovy is significantly more powerful than its predecessors, according to research that helped it garner approval from the FDA in June.

Weve seen 1 to 2 times the amount of weight loss compared to other medications, says Robert Kushner, MD, a researcher at Northwestern University Feinberg School of Medicine who has led semaglutide studies. That's a leapfrog advance.

In fact, semaglutide recipients lost nearly 15% of their body weight on average compared with 2.4% among controls, according to one study of nearly 2,000 patients.

Semaglutide an injectable medication is not entirely new. A synthetic version of a natural hormone that quells appetite, its already used to treat Type 2 diabetes. But the obesity trials, paid for by pharmaceutical company Novo Nordisk, used a much higher dose.

High doses havent been studied long enough to identify long-term side effects, notes Kushner, a paid consultant to Novo Nordisk. But the recent research reported mild-to-moderate gastrointestinal issues that lessened over time.

Now Kushner hopes semaglutide will help spark interest in obesity medications.

Over 40% of U.S. adults have obesity, and the number who are getting a pharmacologic treatment is under 3%, he says. Part of the challenge is educating primary care providers that providing evidence-based obesity care includes consideration of medication."

Randall Bateman, MD, a Washington University School of Medicine in St. Louis (WUSTL) neurologist, is thrilled to have contributed to the first blood test for Alzheimer's disease a devastating condition that affects as many as 5.8 million Americans.

Back in 2017, though, as Bateman geared up to share the discovery that would enable the test, he worried about his peers reaction. After all, scientists were convinced that the blood marker he studied couldnt predict the disease.

But the WUSTL method was much more sensitive and direct than prior approaches. The resultant test called PrecivityAD effectively detects the amyloid plaques that are a hallmark of Alzheimers disease and has proven as accurate as the previously used tools of a spinal tap or positron emission tomography (PET) scan, which are far more costly and complex.

The test, developed by a company called C2N Diagnostics that Bateman co-founded, has been available to physicians since October 2020, when it received approval through a federal lab certification program. It now awaits additional approval from the FDA.

Weve been hoping for a test to diagnose Alzheimers for more than 20 years, says Bateman, WUSTLs Charles F. and Joanne Knight distinguished professor of neurology. Currently, up to half of people with Alzheimers are misdiagnosed.

The road to success in science is paved with hard work and great uncertainty, he adds. Its a real gamble. Youre investing your life in this work, and you hope it will have a positive impact. And then its like, Wow, it worked!

Anger, fear, recurring nightmares, and intense flashbacks are among the many symptoms that can batter patients with post-traumatic stress disorder (PTSD). The condition, which affects about 15 million U.S. adults in a given year, can be extremely difficult to treat.

A potentially groundbreaking PTSD treatment now lies in a seemingly unlikely source: MDMA, better known as the illegal drugs ecstasy and molly that fueled all-night dance raves and caused potentially fatal side effects.

In June, a study in Nature Medicine reported that patients with severe PTSD combat veterans, first responders, and victims of sexual assault and mass shootings, among others experienced significant relief from MDMA.

In fact, two months after treatment, 67% of subjects who received MDMA together with talk therapy no longer qualified for a diagnosis of PTSD. I saw this amazing transformation in patients, says Jennifer Mitchell, PhD, the studys lead author and a University of California, San Francisco, School of Medicine neurology professor.

The treatment involved three eight-hour sessions a month apart during which patients ingested MDMA and processed painful memories and emotions in talk therapy.

MDMA releases a powerful supply of serotonin and stimulates hormones associated with emotional bonding, Mitchell explains. The idea is that it helps patients be open in a way that enables them to connect well with therapists and work through their problems more quickly.

Before the drug can receive FDA approval for PTSD, researchers need to complete one more clinical trial. Even if it succeeds, Mitchell is aware that MDMA still bears stigma from its party drug image.

I hope people are going to be open-minded and look at the data, which included no abuse potential or other serious side effects from MDMA as used in the study. We are talking about use in a controlled, therapeutic situation, she says. Using drugs recreationally is entirely different. Otherwise, people would come back from [the art and community event] Burning Man cured of their psychological issues.

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8 medical advances you may have missed during COVID-19 - AAMC

Editor's Note: Some of the articles described below are not yet available at the PNAS site but are scheduled to be posted this week.

A team from the US and Mexico looks at ties between the gut microbiome and features such as diet, geography, host genetics, and neutral processes like passive dispersal and ecological drift in herbivorous woodrats from seven Neotoma species and more than two dozen wild populations from the southwestern US, along with wild-caught woodrats moved into captive settings. With metabarcoding-based sequencing on microbiome and dietary plant samples, the researchers tracked the effects of host phylogeny and other factors on the gut microbiome, uncovering species-specific gut microbial shifts in captive woodrats. "Although diet and geography influenced natural microbiome structure, the effects of host phylogeny were stronger for both wild and captive animals," they report, adding that the host genetic influence tended to become more pronounced in captivity, while dietary effects waned.

Maternal cannabis use during pregnancy appears to coincide with altered immune-related gene expression in the placenta at birth as well as elevated levels of hair cortisol, anxiety- and hyperactivity-related behaviors, and heart rate variability in three to six-year-old children resulting from the pregnancies, according to another paper in PNAS. Using placental RNA sequencing, behavioral surveys, hair hormone testing, and other approaches, investigators at Icahn School of Medicine at Mount Sinai and City University of New York followed more than 300 mother-child pairs over time, comparing results for children born to 71 mothers who used cannabis during pregnancy and 251 non-users. "Overall," they write, "our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood."

A Columbia University-led team describes a gene-based testing strategy called GeneScan3DKnock that relies on chromatin immunoprecipitation sequencing-based long-range chromatin interaction profiles, gene region-based testing, and a statistical knockoff genotype method. "Through simulations and applications to genome-wide association studies (GWAS) and whole-genome sequencing data for multiple diseases and traits, we show that the proposed test increases the power over state-of-the-art gene-based tests in the literature, identifies genes that replicate in larger studies, and can provide a more narrow focus on the possible causal genes at a locus by reducing the confounding effect of linkage disequilibrium," the authors write, adding that "incorporating genetic variation in distal regulatory elements tends to improve power over conventional tests."

Read the original:
PNAS Papers on Woodrat Microbiome, Maternal Cannabis Use, Gene-Based Testing - GenomeWeb