Category Archives: Gene Medicine

We often talk about genetics as if its set in stone. She just has good genes or He was born with it are common phrases.

However, over the past decade, biochemists and geneticists have discovered that your genetic expression changes over time. Based on environmental factors, certain genes may be strongly expressive while others are dormant.

In fact, a 2016 study of human longevity found that only 25% of health outcomes are attributable to genetics. The other 75% of outcomes are attributable to environmental factors. Among those environmental factors, diet and nutrition play a major role.

An entire branch of scientific research has now exploded around nutrigenomics, the study of the interaction between nutrition and genetics. Scientists now understand that genes set the baseline for how your body can function, but nutrition modifies the extent to which each gene is expressed.

As more data comes in about the types and quality of food that improve health outcomes, high-tech farmers are also entering the nutrigenomics conversation. Using precision agriculture, they hope to produce food thats targeted to deliver a nutrient-rich, genetically beneficial diet.

Implications Of Nutrigenomics

Researchers have found that theres no such thing as a perfect diet. Dietary recommendations are not one-size-fits-all. Each individual needs different nutritional choices for optimal health and gene expression. In addition, each person is different in the extent to which their genes and health are impacted by their diet.

Geneticists and nutritionists are working together to study the dietary levers that most impact genetic expression. If theyre successful, it may be possible to prevent and treat disease through individualized nutrition tailored to your genetic profile. Indeed, you may walk into a doctors office and leave with a dietary prescription customized to your DNA.

In the near future, instead of diagnosing and treating diseases caused by genome or epigenome damage, health care practitioners may be trained to diagnose and nutritionally prevent or even reverse genomic damage and aberrant gene expression, reports Michael Fenech, a research scientist at CSIRO Genome Health and Nutrigenomics Laboratory.

The initial results of nutrigenomics studies are promising. A healthy, personalized diet has the potential to prevent, mitigate, or even cure certain chronic diseases. Nutrigenomics has shown promise in preventing obesity, cancer and diabetes.

If Food Is Medicine, Food Quality Matters

Nutrient abundance or deficiency is the driving factor behind nutrigenomics. Foods that have grown in poor conditions have a lower nutritional density. In turn, eating low-quality foods can have a significant impact on human gene expression. In order to take advantage of the findings of nutrigenomics, consumers need access to high-quality, nutrient-dense foods.

Similar to human health, plant health is impacted by the combination of genes and nutrient intake. Healthy soil, correctly applied fertilization techniques, and other forms of environmental management lead to healthy crops.

However, applying these custom growing techniques at a large scale is a major challenge. Agriculture technology (AgTech) will play a big role in allowing farmers to precisely manage the growing conditions and nutrient delivery for their crops. In turn, this precision farming will make crops more nutritious and targeted for nutrigenomics-driven diets.

Making Food Thats Better For Us

Plant health relies on nutrient uptake from the soil. In order to ensure plants receive the nutrients they need, farmers need to precisely apply additives where theyre needed. With in-ground sensors, advanced mapping of crop quality across a field, and other technologies, farmers can target their applications of water and nutrients to match plant needs. The days of broadly applying generic fertilizer to entire fields are coming to an end.

Farmers play an integral role in providing access to diverse, nutritious food, explains Remi Schmaltz, CEO of Decisive Farming. Nutrient deficiency in plants and the soil can contribute to the deficiencies found in humans. The opportunity exists to address these deficiencies through precision nutrition delivered by the agriculture sector.

Additionally, CRISPR and other technologies allow us to experiment with the genetic makeup of plants, increasing nutrition and flavor, both pluses for consumers. In recent years, genetic modification has produced disease-resistant bananas, more flavorful tomatoes, lower gluten wheat, non-browning mushrooms and sustainable rice. While there has been a lot of skepticism over genetically-modified crops, multiple studies have shown that GMOs are safe for consumption and can even improve plant health and nutrition.

Using Biochemistry And Big Data To Create Better Food And Healthier People

Nutrigenomics will completely change how we think about health and disease prevention. Indeed, personalized diet recommendations that are tailored to your genes could be a new form of medicine for chronic illnesses.

Nevertheless, a key part of making nutrigenomics effective is having access to high-quality, nutrient-dense foods. AgTech is using the internet of things, AI, precision farming and gene editing to make nutrient-dense food more readily available. The benefits to public health from these efforts could change the way we think about medicine, longevity and what it means to be healthy.

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Food As Medicine: What Biochemistry And Genetics Are Teaching Us About How To Eat Right - Forbes

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New research links a genetic anomaly and some forms of SIDS, or sudden infant death syndrome, which claims the lives of more than 3,000 infants a year.

The research, published in Nature Communications, focuses on mitochondrial tri-functional protein deficiency, a potentially fatal cardiac metabolic disorder caused by a genetic mutation in the gene HADHA.

Newborns with this genetic anomaly cant metabolize the lipids found in milk, and die suddenly of cardiac arrest when they are a couple months old. Lipids are a category of molecules that include fats, cholesterol, and fatty acids.

There are multiple causes for sudden infant death syndrome, says Hannele Ruohola-Baker, professor of biochemistry at the University of Washington School of Medicine, who is also associate director of the Medicine Institute for Stem Cell and Regenerative Medicine.

There are some causes which are environmental. But what were studying here is really a genetic cause of SIDS. In this particular case, it involves defect in the enzyme that breaks down fat.

Lead author Jason Miklas, who earned his PhD at the University of Washington and is now a postdoctoral fellow at Stanford University, says he first came up with the idea while researching heart disease and noticed a small research study that had examined children who couldnt process fats and who had cardiac disease that was not readily explained.

So he and Ruohola-Baker started looking into why heart cells, grown to mimic infant cells, died in the petri dish where they were growing.

If a child has a mutation, depending on the mutation the first few months of life can be very scary as the child may die suddenly, Miklas says. An autopsy wouldnt necessarily pick up why the child passed but we think it might be due to the infants heart stopping to beat.

Were no longer just trying to treat the symptoms of the disease, Miklas says. Were trying to find ways to treat the root problem. Its very gratifying to see that we can make real progress in the lab toward interventions that could one day make their way to the clinic.

In MTP deficiency, the heart cells of affected infants dont convert fats into nutrients properly, resulting in a build-up of unprocessed fatty material that can disrupt heart functions. More technically, the breakdown occurs when enzymes fail to complete a process known as fatty acid oxidation. It is possible to screen for the genetic markers of MTP deficiency; but effective treatments remain a ways off.

Ruohola-Baker says the latest laboratory discovery is a big step towards finding ways to overcome SIDS.

There is no cure for this, she says. But there is now hope, because weve found a new aspect of this disease that will innovate generations of novel small molecules and designed proteins, which might help these patients in the future.

One drug the group is focusing on is Elamipretide, used to stimulate hearts and organs that have oxygen deficiency, but barely considered for helping infant hearts, until now. In addition, prospective parents can undergo screening to see if there is a chance that they could have a child who might carry the mutation.

Ruohola-Baker has a personal interest in the research: one of her friends in Finland, her home country, had a baby who died of SIDS.

It was absolutely devastating for that couple, she says. Since then, Ive been very interested in the causes for sudden infant death syndrome. Its very exciting to think that our work may contribute to future treatments, and help for the heartbreak for the parents who find their children have these mutations.

The National Institutes of Health, the Academy of Finland, Finnish Foundation for Cardiovascular Research. Wellstone Muscular Dystrophy Cooperative Research Center, Natural Sciences and Engineering Research of Canada, an Alexander Graham Bell Graduate Scholarship, and the National Science Foundation funded the work.

Source: University of Washington

Original Study DOI: 10.1038/s41467-019-12482-1

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Some cases of SIDS may have this genetic cause - Futurity: Research News

Nobel Assembly member, Randall Johnson (R), speaks to announce the winners of the 2019 Nobel Prize in Physiology or Medicine (L-R) Gregg Semenza of the US, Peter Ratcliffe of Britain and William Kaelin of the US, seen on a screen during a press

Dr. William G. Kaelin, Jr., Sir Peter J. Ratcliffe, and Dr. Gregg L. Semenza now have an extra line to add to their resumes or LinkedIn profiles. The Nobel Assembly announced on Monday that these three physician-scientists have been awarded the 2019 Nobel Prize in Physiology or Medicine for helping find ways that your body can sense and adapt to different levels of oxygen:

Winning this Prize will bring each of them a third of a 9 million Swedish kronor or $907,000 cash prize and an amazing retort to anyone else who may brag too much at a cocktail party. Of course, the Nobel Prize isnt their first accomplishment but instead serves as a tribute to three careers that have brought discoveries that may lead to new treatments for anemia and cancer.

Kaelin is currently a Professor at Harvard Medical School and the Dana-Farber Cancer Institute. Born in 1957, he eventually got his M.D. from Duke University, Durham, and trained in internal medicine and oncology at Johns Hopkins University and the Dana-Farber Cancer Institute.

Ratcliffe wasnt a Sir yet when he was born in 1954. After studying medicine at Cambridge University and completing nephrology training at Oxford, he subsequently became the Nuffield Professor of Clinical Medicine at Oxford and the Director of Clinical Research at the Francis Crick Institute in London, Director for Target Discovery Institute at Oxford, a Member of the Ludwig Institute for Cancer Research, and knighted.

Semenza is a Professor of Medicine at Johns Hopkins University and Director of the Vascular Research Program at the Johns Hopkins Institute for Cell Engineering. He was born in 1956, obtained both an MD and a PhD from the University of Pennsylvania and completed residency training in pediatrics at Duke University and a post-doc at Johns Hopkins University.

To understand the importance of their discoveries, its important to understand the how your body needs complex ways to regulate oxygen levels. As you first learn when you try to put a sock over your head (dont try this, by the way), oxygen is pretty fundamental to everything that you do. Without it, the trillions and trillions of cells in your body couldnt survive and function. Each cell uses oxygen to help break down nutrients into energy. Thus, no oxygen, no energy. No energy, no cells, and no you. And no Instagramming and texting.

The trouble is oxygen, like macaroni and cheese and anything else good in life, isnt always present at the levels that you and all your cells would like. Oxygen levels can fluctuate in the air that you breathe and in different parts of your body. The ability of each of your cells to get oxygen can depend heavily on location, location, location, as the old real estate saying goes.

Think of your body as a large and complex metropolitan area with many different neighborhoods. Red blood cells are like little Ubers picking up oxygen at your lungs and then carrying the molecules of oxygen along your blood vessels, which serve as roads to different parts of your body. Just as the roads are different in different parts of the Boston area, the density and networks of blood vessels vary throughout your body. Thus, not every part of your body will always get the same amount of blood and oxygen. These differences can be exacerbated when your blood circulation in general decreases, such as when you are lying on the coach after eating way too much macaroni and cheese, or blood flow in a particular part of your body gets interrupted, such as when you are bleeding or have a blood clot.

Therefore, like a well-run city, your body needs ways of sensing whats going on in each of the neighborhoods and adjusting oxygen levels accordingly. One way of adjusting your bodys oxygen supply in general is by changing your breathing rate. The carotid arteries are the major blood vessels in your neck and the ones that often spurt blood in slasher horror movies. These arteries include structures called carotid bodies that can check the oxygen levels in the passing blood. If oxygen levels are too low, the carotid bodies sends signals through nerves to increase your breathing rate. If the oxygen levels are too high, the carotid bodies will signal to slow your breathing. While this may help the overall amount of oxygen getting into your lungs and blood circulation, it alone cant monitor and adjust the oxygen thats getting to more local levels throughout your body.

Another thing that regulates oxygen levels is EPO, which is pronounced like Emo but with a p instead of an m. EPO is short for erythropoietin, a hormone that can stimulate your body to produce more red blood cells and thus have more Ubers to deliver oxygen. When EPO levels rise, erythropoiesis, a fancy name for red blood cell production, increases. However, before the work of Semenza, Ratcliffe, and Kaelin and their respective teams, it wasnt clear exactly how oxygen levels were able to affect EPO levels.

Here is Dr. Gregg L. Semenza M.D., Ph.D at a press conference at Johns Hopkins Hospital after learning that he had won the Nobel Prize for Medicine. (Photo by John Strohsacker/Getty Images)

In the 1990s, both Semenzas and Ratcliffes teams found that all types of body tissues have the ability to sense oxygen levels, not just the kidney cells that produce EPO. Semenzas team found DNA sequences near the genes that code for EPO and continued to search for ways that the EPO gene is regulated. A HIF, HIF hooray moment came when they found a protein complex, which they named HIF for hypoxia-inducible factor. Hypoxia is a medical term for low oxygen. Thus, when George Costanza said on an episode of Seinfeld, oxygen, I need oxygen, he could have said, I have hypoxia, instead. Thus, hypoxia-induced means something that will be stimulated by low oxygen levels. The team eventually realized that this protein complex actually consists of two different proteins that can bind DNA, which they named HIF-1 and ARNT.

Experiments showed that when oxygen levels are high, cells have very low levels of HIF-1 because the HIF-1 thats produced gets rapidly degraded. However, when oxygen levels dip low, HIF-1, in the words of the Supremes, keeps on hanging on and doesnt degrade as quickly. Therefore, there is more HIF-1 around to stimulate the EPO genes to produce more EPO.

The difference seemed to be ubiquitin. Ubiqutin can bind to HIF-1 and mark it to go bye bye, which is what host of the game show The Weakest Link says to contestants before they must exit. In this way, ubiquitin serves as a label to say, please get rid of this.

But it still wasnt yet clear how lower oxygen levels could keep ubiquitin from binding to HIF-1. This is when Kaelins team entered the mix. They had been studying something seemingly unrelated, von Hippel-Lindaus disease, which is often abbreviated VHL disease. This is a condition that is inherited and includes mutations in the VHL gene. They observed that normally the VHL gene codes for proteins that seem to prevent certain cancers from developing. In VHL disease, mutations prevent this gene from working properly, allowing a number of different cancers to emerge.

William G Kaelin Jr., MD, speaks at the Dana Farber Cancer Institute on October 7, 2019 in Boston, Massachusetts. (Photo by Scott Eisen/Getty Images)

Here is an example of how starting on one path doesnt necessarily lead you to where you thought you would go and how the most interesting things in life can be unexpected. Kaelins team eventually realized that such cells with mutations in the VHL gene also expressed abnormally high levels of hypoxia-regulated genes, which made them wonder whether VHL played a role in regulating the response to low oxygen levels. This wasnt totally surprising since cancer cells also need oxygen to survive, and such cells cant always get the same access to blood and oxygen when they sit deep in the middle of tumors.

Indeed, additional work showed that the VHL genes produce proteins that then help connect ubiquitin to HIF-1 and thus label HIF-1 for destruction. In essence, VHL is like a warehouse inventory manager using ubiquitin as a label for get rid of this. But the scientists were still left with the question, how do oxygen levels influence whether VHL labels HIF-1 with ubiquitin?

The mystery step turned out to be prolyl hydroxylation. What-yl what-xylation? This is a process by which enzymes (calledprolyl hydroxylases) add hydroxyl groups to two parts of the HIF-1 protein. A hydroxyl group is a combination of an oxygen atom (designated by O) and hydrogen atom (designated by H) and symbolized by -OH. This process is necessary for the HIF-1 protein to be labeled and destroyed. Think of it as OH, lets get rid of this. When oxygen levels are lower, many HIF-1 proteins may not get this OH thus preventing the VHL-ubiquitin labeling process from occurring. The work of Kaelin, Semenz, and their teams thus found the final piece of the puzzle and said OH, thats how it works.

You can see how prolyl hydroxylases could play major roles in the treatment of anemia (which occurs when your red blood cell counts are low) and various cancers with their ability to ultimately regulate red blood cell production and oxygen delivery. Again, cancer cells need oxygen to survive. Starve them of oxygen and you may have a way of killing them.

It didnt seem like this trio of investigators started their independent scientific careers with the intent of all of this happening. While science needs some direction, you cant just go into a lab and start mixing things together, the best science often emerges from exploration and being curious and open to different possibilities. Semenza, Ratcliffe, and Kaelin clearly had the minds and abilities to do such science but they also had the time and resources to do so. Like body tissues do for varying oxygen levels, science and scientists need to have the ability and opportunity to adapt to what they may find. This may not occur as often these days when research funding is more limited and people and institutions are pushing for immediate returns on work. For the eventual benefit of humankind, scientists need to be able to say, OH, lets try this, and then find OH, what do we have here?

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The 2019 Nobel Prize In Medicine: Here Is What Won The Award - Forbes

Next-generation sequencing techniques to determine an individuals unique genetic code gave rise to personalized treatments. Single-cell sequencing is the next step towards making precision medicine more accurate.

Each cell in our body is unique. Even genetically identical cells can behave differently in response to a certain treatment. With next-generation sequencing, scientists can study how the average cell within a group behaves. However, this can lead to erroneous conclusions.

It is like population surveys which tell us the average American family has 1.2 children. Thats useless. Thats not helpful. Not a single family has 1.2 children, stated Christoph Lengauer, CEO of Celsius Therapeutics, in an interview with STAT News. His company has raised more than 60M to develop precision therapies using machine learning.

Single-cell sequencing, by contrast, can indicate which family has six children, and which has just one and a dog, Lengauer said. Its orders of magnitude more granular.

This is a huge paradigm shift. Single-cell sequencing was recognized as method of the year by Nature in 2013. Since then, the number of publications from both academia and the industry exploded.

In recent years, there has been a shift in the technology available to perform single-cell sequencing. Fluidigm used to hold the bulk of the market with products across the entire workflow but is currently suffering from poor sales due to new competitors.

At the forefront is US-based 10X Genomics, founded in 2012, which registered a 20-fold revenue increase between 2015 and 2017. Its sequencing platform allows large populations of cells to be separated and analyzed with high resolution. The company is also developing a technology to study how cells are positioned in 3D which could be used to see how tumors grow and expand.

Another contender is the alliance between two giants, Bio-Rad Laboratories and Illumina. They announced in January 2019 a joint single-cell sequencing solution that streamlines the whole workflow. Mission Bio, a spin-off from the University of California San Francisco is selling a single-cell sequencing platform that targets clinical applications with a lower price per run compared to its competitors.

Despite the rapid market growth, the use of single-cell sequencing is so far limited to a narrow circle of initiates. Over the past years, academic facilities have started providing single-cell sequencing services to researchers. For example, the technology is used at the Institut Curie in Paris to study cancer cells.

More recently, companies have started working in this area, often using technology initially developed in academia to identify new biomarkers and drug targets. All seem to have a common goal: personalized medicine.

Research on most diseases related to genetic or epigenetic mutations could benefit at some point from single-cell sequencing. There are already scientific publications applying this technology in microbiology, neurology, immunology, digestive and urinary conditions.

Among them, oncology is probably the most promising and mature application. Previously, bulk analysis of cells from a tumor biopsy only gave information on the predominant type of cells. In contrast, single-cell sequencing can provide information about other tumor cells, which might be resistant to a certain therapy and result in a relapse after the first line of treatment.

This technique is highly sensitive and is able to detect rare cell types from limited amounts of sample material. Combined with technology to isolate circulating tumor cells from a blood sample, single-cell sequencing can be used to select patients in personalized medicine trials.

IsoPlexis is one of the very few companies with an advanced program to apply single-cell sequencing to proteomic studies looking at the role of protein expression in cancer. The company is developing a technology to measure the levels of a dozen molecules secreted by immune cells that are primed to recognize and attack a tumor. Last year, this was used to predict, for the first time, the response that a person with blood cancer will have to CAR T-cell therapy. The company claims that it could also be applied to cancer patients treated with checkpoint inhibitor immunotherapy.

Single-cell sequencing can also be combined with CRISPR gene editing to make elaborated large-scale studies of how a genetic modification affects cell behavior. The Austrian company Aelian Biotechnology is combining both techniques to observe gene functions with single-cell resolution, establishing a new paradigm for next-generation CRISPR screening. This approach has broad applications, including identifying novel drug targets or studying unknown mechanisms of actions of drugs.

Either for research or clinical diagnostics, single-cell sequencing remains challenging and is far from being used routinely. One of the main reasons is that single-cell collection is tricky, as the amount of sample material used is low but the analysis still requires a sufficient amount of cells to make sure all cell types are represented. The time it currently takes to complete an experiment is another major concern. Companies developing single-cell sequencing technology need to work on creating streamlined and optimized workflows that limit these problems.

Although experimental methods for single-cell sequencing are increasingly accessible to laboratories, handling the data analysis remains challenging. There are currently limited guidelines as to how to define quality control metrics, the removal of technical artifacts, and the interpretation of the results. With larger experiments, the data analysis burden increases.

Single-cell data requires the analysis of millions of data points for a single tumor, said Andrei Zinovyev, who leads a machine learning project focusing on single-cell data analysis at the Institut Curie in Paris.

There are many software tools developed by academics, mostly available in open source. However, their use is limited to a small community of researchers that have been able to successfully combine advanced bioinformatics and statistical skills with in-depth knowledge of the biological systems they study. Companies such as 10X Genomics and Fluidigm also provide software tools, but this area remains in its infancy and gold-standard tools have yet to be developed.

For single-cell analysis to spread to a broader community, user-friendly analysis tools are needed. In this area, Swiss startup Scailyte is developing an AI-based solution to discover biomarkers from single-cell data, analyzing complex datasets in just a few hours. The US startup Cellarity is also working in this area, seeking to combine single-cell sequencing with artificial intelligence and CRISPR gene editing.

The use of single-cell sequencing is limited due in part to its high cost. Most of the instruments and reagents needed are costly. For someone looking to incorporate single-cell sequencing into their laboratory, 10X Genomics for example sells its instruments for about 70,000. A typical run, including cell isolation and sequencing, can cost anywhere between 3,000 and 10,000 per sample, depending on the number of cells.

Due to the high cost, it is becoming popular for laboratories with the equipment to offer single-cell sequencing and analysis as a service. The US company Mission Bio is tackling this issue, aiming to reduce the cost to between $1,000 and $2,000 for a typical run.

As is mostly the case in any area with a huge market potential, intellectual property can cause conflict, which can negatively impact the development of new technologies. For example, back in 2015, Bio-Rad sued 10X Genomics for patent infringement, and the jury determined it would have to pay 21M in damages. Furthermore, 10X Genomics could not sell their products to new customers, being therefore limited to servicing historical clients with all past and future sales subject to a 15% royalty.

Several months later, the US company Becton Dickinson also sued 10X Genomics. After that, the company decided to build a new piece of equipment to reinforce its intellectual property position. In September, 10X Genomics countersued Becton Dickinson.

The single-cell sequencing market experienced a growth spike between 2017 and 2018 due to several key stakeholders entering the market. But we are only at the beginning. According to most business reports, this market is expected to see a 300% growth, reaching a size of almost 1.4B by 2023.

Competitors are innovating at an insane rate to take the lead, but there is still a long way to go before single-cell sequencing can be widely used. A huge amount of investment would be needed to fully unlock its potential for research, drug discovery, and diagnostics. Nonetheless, the field has momentum and once it tackles the challenges, there is no doubt that single-cell sequencing will pave the way to breakthrough innovations in personalized medicine.

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Single-Cell Sequencing: Paving the Way for Precision... - Labiotech.eu

ZUG, Switzerland and CAMBRIDGE, Mass., Oct. 15, 2019 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, and KSQ Therapeutics, a biotechnology company using CRISPR technology to enable the companys powerful drug discovery engine to achieve higher probabilities of success in drug development, today announced a license agreement whereby CRISPR Therapeutics will gain access to KSQ intellectual property (IP) for editing certain novel gene targets in its allogeneic oncology cell therapy programs, and KSQ will gain access to CRISPR Therapeutics IP for editing novel gene targets identified by KSQ as part of its current and future eTIL (engineered tumor infiltrating lymphocyte) cell programs. The financial terms of the agreement are not being disclosed.

We are thrilled to gain access to CRISPR Therapeutics foundational IP estate through this agreement, said David Meeker, M.D., Chief Executive Officer at KSQ Therapeutics. Our eTIL programs involve editing gene targets in human TILs that were discovered at KSQ by applying our proprietary CRISPRomics approach to immune cells in multiple in vivo models. This agreement clears an important path for us to be able to bring these programs through development and commercialization, leveraging CRISPR Therapeutics proprietary editing technology.

The gene targets within the scope of the license agreement were identified using KSQs proprietary CRISPRomics drug discovery engine, which allows genome-scale, in vivo validated, unbiased drug discovery. These specific targets were uncovered in screens to identify genetic edits that could enhance the functionality and quality of adoptive cell therapies in oncology.

KSQ has built an industry-leading platform to screen for novel gene targets using its technology, and has identified a group of targets that could help unlock the full potential of adoptive cell therapy in oncology, said Samarth Kulkarni, Ph.D., Chief Executive Officer at CRISPR Therapeutics. As a result of this license agreement, CRISPR Therapeutics will have the opportunity to bring these novel targets into our leading allogeneic CAR-T development platform to further strengthen our future programs in this important therapeutic area.

About KSQ TherapeuticsKSQ Therapeutics is using CRISPR technology to enable the companys powerful drug discovery engine to achieve higher probabilities of success in drug development. The company is advancing a pipeline of tumor- and immune-focused drug candidates for the treatment of cancer, across multiple drug modalities including targeted therapies, adoptive cell therapies and immuno-therapies. KSQs proprietary CRISPRomics drug discovery engine enables genome-scale, in vivo validated, unbiased drug discovery across broad therapeutic areas. KSQ was founded by thought leaders in the field of functional genomics and pioneers of CRISPR screening technologies, and the company is located in Cambridge, Massachusetts. For more information, please visit the companys website at http://www.ksqtx.com.

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 AG, 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 London, United Kingdom. For more information, please visit http://www.crisprtx.com.

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 regarding CRISPR Therapeutics expectations about any or all of the following: (i) the intellectual property coverage and positions of CRISPR Therapeutics, its licensors and third parties and (ii) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and 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 outcomes for each CRISPR Therapeutics planned clinical trials and studies may not be favorable; that one or more of CRISPR Therapeutics internal or external product candidate programs will not proceed as planned for technical, scientific or commercial reasons; that future competitive or other market factors may adversely affect the commercial potential for CRISPR Therapeutics product candidates; uncertainties inherent in the initiation and completion of preclinical studies for CRISPR Therapeutics product candidates; availability and timing of results from preclinical studies; whether results from a preclinical trial will be predictive of future results of the future trials; uncertainties about regulatory approvals to conduct trials or to market products; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics most recent annual report on Form 10-K, 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:Jennifer PaganelliWCG on behalf of CRISPR+1 347-658-8290jpaganelli@wcgworld.com

KSQ Contact:Michael LampeTel: 484-575-5040michael@scientpr.com

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CRISPR Therapeutics and KSQ Therapeutics Announce License Agreement to Advance Companies' Respective Cell Therapy Programs in Oncology - BioSpace

A phase I/II trial run by the Dutch company ProQR has found that its RNA therapy could significantly improve the vision of people with Lebers congenital amaurosis, a rare genetic disease for which there is no treatment.

The RNA drug, called sepofarsen, is designed to treat people with a specific mutation in a gene called CEP290. This mutation causes the RNA transcript of the gene to have the wrong three-dimensional structure, blocking its translation into a protein. This, in turn, causes vision loss in the first few years of life.

Sepofarsen is an RNA molecule that specifically binds to the faulty RNA transcript to stabilize its structure and allow the retinal cells to produce the protein.

In a phase I/II trial run in the US and Belgium, the RNA drug significantly improved the vision of children and adults with this condition over a 1-year period.

In some cases the patients vision improved to a level that could be deemed life-changing, said Stephen Russell, a professor at the University of Iowa and principal investigator of the study.

The effects of the drug were stronger on patients that had a certain level of visual acuity to start with. These are ultimately the target population of ProQR, which is already running a phase II/III study that will follow the response of 30 patients over the course of 2 years. Results from that trial are expected in 2021 and will inform whether the FDA and the EMA approve the drug or not.

The main goal of the phase I/II trial was to determine the safety of sepofarsen. While the treatment caused cataracts in eight out of 11 patients, all of those who underwent lens replacement surgery recovered their vision. Other side effects of the drug on the eye were manageable with additional treatments.

There are hundreds of different genetic mutations that cause blindness. The rarity of each of these conditions individually has meant that many of them have no treatment available. In recent years, gene therapy has become an option to treat some of these conditions; the first was Luxturna, approved in 2017. Another approach that has only entered the first clinical trial this year is CRISPR gene editing, which is being carried out by Editas Medicine and Allergan.

In contrast, ProQRs RNA drug could provide an alternative approach that does not involve a permanent change in the DNA of retinal cells. The drug is instead delivered to the eye via injection every 6 months.

Still, each of these new treatments can only address one specific mutation of the many causing blindness. As all these new technologies are developed, together they could eventually provide solutions covering a wide range of these mutations.

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RNA Therapy Improves Vision in Untreatable Genetic... - Labiotech.eu

Burn specialists at Massachusetts General Hospital are the first in the world to successfully use live-cell, genetically engineered pig skin to temporarily close a burn wound in a human patient but the breakthrough has drawn opposition from People for the Ethical Treatment of Animals.

The ultimate holy grail is the end to the worlds organ shortage, that would be the holy grail, this has come at a time when genetic editing is really hot and what we could do in years, we can do in weeks, said Dr. Jeremy Goverman of the MGH Sumner Redstone Burn Service.

The pig tissue, known as xenoskin, was transplanted directly onto a human burn wound next to a larger piece of human skin.

Five days later, surgeons removed the human skin and the pig tissue to see that both grafts were stuck to the wound bed and were indistinguishable from each other.

Following the procedure, the burn wound was then treated further with a skin graft taken from the patients thigh. Healing progressed well and the patient will return to work soon.

The goal is to replace skin with xenoskin thats like it enough that it doesnt get rejected, said Goverman. Down the line we hope to ultimately create something thats not temporary.

The biggest push now is actually decreasing your donor site size and decreasing how much skin you have to harvest, said Goverman.

Patients who receive this type of graft typically have severe burns that require more than one operation and about a week of hospitalization.

Weve been using dressing like this in the past, we just havent been able to use anything with live cells. The live cells have all the appropriate factors that could really stimulate and regenerate and close our wounds for us, said Goverman.

MGH worked with Boston-based XenoTherapeutics, which designed the safety protocols for the special live-pig tissue graft.

Paul Holzer, CEO of XenoTherapeutics said, We have taken a small but unprecedented step in bringing xenotransplantation from theory to therapy, one that we hope will advance this promising field of medicine and benefit patients around the world.

Human skin grafts are subject to a national shortage and can be expensive, therefore using the pig skin can serve as a viable alternative, according to MGH.

But Alka Chandna, vice president of laboratory investigations cases at PETA, said there is no shortage of donated skin grafts.

Its categorically unethical to steal organs from another sentient being whos still using them. Pigs are individuals, not warehouses for spare parts, said Chandna.

Chandna said, Tinkering with the genes of these intelligent, sensitive beings to turn them into organ factories is a waste of lives, time and money and the suffering caused is unimaginable.

The advancement of the procedure reaches back decades to genetically modified pigs that were developed in the 1990s at MGH by Dr. David Sachs.

The modifications removed a gene specific to pigs and not present in humans, allowing the pig skin to appear less foreign to the human immune system.

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MGH doctors perform first-ever live-cell pig skin graft to burn patient - Boston Herald

The company expands its Scientific Advisory Board with four additional RNA splicing, genetics, and disease experts, who join SAB Chair Professor Tyler Jacks & special advisor Professor Phil Sharp as well as several other internationally-recognized SAB members.

WALTHAM, Mass., Oct. 15, 2019 /PRNewswire/ -- Skyhawk Therapeutics, Inc. ("Skyhawk"), a drug discovery and development company focused on revolutionizing disease treatment with small molecules that modify RNA expression, today announced the appointment of four additional internationally recognized experts in RNA biology and disease to its Scientific Advisory Board.

Skyhawk Therapeutics, Inc. (PRNewsfoto/Skyhawk Therapeutics)

"I am thrilled that we have assembled such a stellar group of RNA biology and human disease experts for Skyhawk's Scientific Advisory Board," said Prof. Tyler Jacks, Director of MIT's Koch Institute for Integrative Cancer Research and Chair of Skyhawk's SAB. "We look forward to having their combined knowledge and wisdom help guide Skyhawk's research and development efforts, to progress even more rapidly towards groundbreaking new approaches and therapies for patients with a variety of difficult-to-treat diseases."

Prof. Ben Blencowe is an internationally recognizedRNA biologist who has made pioneering contributions to the understanding of the molecular mechanisms controlling alternative splicing and their roles in evolution, development and disease. He holds the Banbury Chair of Medical Research and is Professor in the Donnelly Centre at the University of Toronto; he also serves as Director of the Donnelly Sequencing Centre. Prof. Blencowe has received numerous awards and honors for his research excellence and was recently elected Fellow of the Royal Society (UK).

Dr. Ben Ebert is the George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School, and Chair of Medical Oncology at the Dana-Farber Cancer Institute. His research focuses on the genetics, biology, and therapy of myeloid malignancies. His work has led to the characterization of clonal hematopoiesis as a pre-malignant state for hematologic malignancies, and elucidation of the mechanism of action of lenalidomide and related molecules that induce degradation of specific proteins. Dr. Ebert has served as president of the American Society for Clinical Investigation and is an elected member of the National Academy of Medicine and the Association of American Physicians.

Prof. Jeannie T. Lee is Professor of Genetics and Pathology at Harvard Medical School, the Blavatnik Institute, and the Massachusetts General Hospital. She specializes in the study of epigenetic regulation by long noncoding RNAs and uses X-chromosome inactivation as a model system. Prof. Lee also translates basic knowledge to find treatments for genetic disorders and co-founded two publicly traded companies Translate Bio and Fulcrum Therapeutics. She is a Member of the National Academy of Sciences, a 2018 Harrington Rare Disease Scholar, the 2016 recipient of the Lurie Prize, a 2016 recipient of the Centennial Award from the Genetics Society of America, the 2010 awardee of the Molecular Biology Prize from the National Academy of Sciences, and a Fellow of the American Association for the Advancement of Science.

Prof. Maurice Swanson is an expert on the regulation of RNA alternative processing during mammalian development and how this regulation is disrupted in neurological and neuromuscular diseases, including some types of muscular dystrophy and amyotrophic lateral sclerosis (ALS). Prof. Swanson is a Professor in the Department of Molecular Genetics and Microbiology at the University of Florida College of Medicine and Associate Director of the Center for NeuroGenetics. His lab focuses on the functions of repetitive DNA elements, particularly microsatellites or short tandem repeats (STRs), in RNA-mediated disorders. An important objective of these studies is to enhance tissue regeneration following treatment modalities designed to block the toxicity of STR.

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These four new members join Skyhawk's existing Scientific Advisory Board members & advisors including:

About Skyhawk TherapeuticsSkyhawk Therapeutics is committed to discovering, developing and commercializing therapies that use its novel SkySTAR (Skyhawk Small molecule Therapeutics for Alternative splicing of RNA) platform to build small molecule drugs that bring breakthrough treatments to patients.

For more information visit: http://www.skyhawktx.com, https://twitter.com/Skyhawk_Tx, https://www.linkedin.com/company/skyhawk-therapeutics/

SKYHAWK MEDIA CONTACT:Anne Deconinckanne@skyhawktx.com

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World Renowned Experts Appointed to Skyhawk Therapeutics Scientific Advisory Board - Yahoo Finance

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Mouse study shows immune cells drive brain damage

A neuron containing tangles of tau protein is surrounded by immune cells known as microglia in this computer-generated image. A study from Washington University School of Medicine in St. Louis has found that microglia drive neurodegeneration in diseases, including Alzheimer's disease, that are linked to tau protein. Targeting microglia may help treat such diseases.

Messy tangles of a protein called tau can be found in the brains of people with Alzheimers disease and some other neurodegenerative diseases. In Alzheimers, the tangles coalesce just before tissue damage becomes visible in brain scans and people start to become forgetful and confused.

Now, a new study has found that brain immune cells called microglia which are activated as tau tangles accumulate form the crucial link between protein clumping and brain damage. The research, published Oct. 10 inthe Journal of Experimental Medicine, shows that eliminating such cells sharply reduces tau-linked brain damage in the mice and suggests that suppressing such cells might prevent or delay the onset of dementia in people.

Right now many people are trying to develop new therapies for Alzheimers disease, because the ones we have are simply not effective, said senior authorDavid Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of theDepartment of Neurology. If we could find a drug that specifically deactivates the microglia just at the beginning of the neurodegeneration phase of the disease, it would absolutely be worth evaluating in people.

Under ordinary circumstances, tau contributes to the normal, healthy functioning of brain neurons. In some people, though, it collects into toxic tangles that are a hallmark of neurodegenerative diseases such as Alzheimers and chronic traumatic encephalopathy, a progressive brain disease often diagnosed in football players and boxers who have sustained repeated blows to the head. Holtzman and colleagues previously had shown that microglia limit the development of a harmful form of tau. But the researchers also suspected that microglial cells could be a double-edged sword. Later in the course of the disease, once the tau tangles have formed, the cells attempts to attack the tangles might harm nearby neurons and contribute to neurodegeneration.

To understand the role of microglial cells in tau-driven neurodegeneration, Holtzman, first author and postdoctoral researcher Yang Shi, PhD, and colleagues studied genetically modified mice that carry a mutant form of human tau that easily clumps together. Typically, such mice start developing tau tangles at around 6 months of age and exhibiting signs of neurological damage by 9 months.

Then, the researchers turned their attention to the gene APOE. Everyone carries some version of APOE, but people who carry the APOE4 variant have up to 12 times the risk of developing Alzheimers disease compared with those who carry lower-risk variants. The researchers genetically modified the mice to carry the human APOE4 variant or no APOE gene. Holtzman, Shi and colleagues previously had shown that APOE4 amplifies the toxic effects of tau on neurons.

For three months, starting when the mice were 6 months of age, the researchers fed some mice a compound to deplete microglia in their brains. Other mice were given a placebo for comparison.

The brains of mice with tau tangles and the high-risk genetic variant were severely shrunken and damaged by 9 months of age as long as microglia were also present. If microglia had been eliminated by the compound, the mices brains looked essentially normal and healthy with less evidence of harmful forms of tau despite the presence of the risky form of APOE.

Further, mice with microglia and mutant human tau but no APOE also had minimal brain damage and fewer signs of damaging tau tangles. Additional experiments showed that microglia need APOE to become activated. Microglia that have not been activated do not destroy brain tissue or promote the development of harmful forms of tau, the researchers said.

Microglia drive neurodegeneration, probably through inflammation-induced neuronal death, Shi said. But even if thats the case, if you dont have microglia, or you have microglia but they cant be activated, harmful forms of tau do not progress to an advanced stage, and you dont get neurological damage.

The findings indicate that microglia are the linchpin of the neurodegenerative process and an appealing target of efforts to prevent cognitive decline in Alzheimers disease, chronic traumatic encephalopathy and other neurodegenerative diseases. The compound Holtzman and Shi used in this study has side effects that make it a poor option for drug development, but it could point the way to other compounds more narrowly tailored to microglia.

If you could target microglia in some specific way and prevent them from causing damage, I think that would be a really important, strategic, novel way to develop a treatment, Holtzman said.

Shi Y, Manis M, Long J, Wang K, Sullivan PM, Remolina J, Hoyle R, Holtzman DM. Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model. Journal of Experimental Medicine.Oct. 10, 2019. DOI: 10.1084/jem.20190980

This study is supported by the National Institutes of Health (NIH), grant numbers NS090934 and AG047644; JPB Foundation; and the Cure Alzheimers Fund.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Targeting immune cells may be potential therapy for Alzheimer's - Washington University School of Medicine in St. Louis

For the last seven years, a rare neurological disorder ravaged Mitchell Herndon's body.

As the condition a genetic mutation diagnosed in only a few people in the world robbed the Missouri teen of his ability to walk, took his hearing and then his eyesight, Herndon made a decision: If the disease killed him, he would donate his body to science in the hopes of saving others.

Last Wednesday, just days before a potentially life-saving drug would have been made available to him, Herndon, 19, died. Abiding by his wishes, Herndon's family chose to gift his body to Washington University in St. Louis for research into neuro-muscular diseases something that doctors say will be invaluable for advancing the understanding of more than his own disorder.

"It's an incredible tool which he has donated. This will have an impact for many people that get identified with his condition in the future, as well as other people with other neurodegenerative conditions" such as amyotrophic lateral sclerosis (ALS), or possibly Alzheimer's and Parkinson's diseases, said Dr. Bob Bucelli, the neurologist who treated Herndon for the past year and an associate professor of neurology at Washington University School of Medicine in St. Louis. "It's a limitless resource that he's given and incredible what he's offered the medical community by doing that."

In May 2019, Herndon was the subject of an NBC News Digital documentary viewed 4 million times about what it was like to be living with a mysterious disease that kept progressing as doctors raced to try to save him.

Herndon, of Affton, Missouri, had been a healthy, athletic child when he started experiencing difficulty moving his legs at age 12. He was eventually diagnosed with a rare mutation of the ACOX1 gene, which until recently had only been diagnosed in one other person: a teenage girl in South Korea who is unable to communicate. Because the condition is so uncommon, it does not yet have a name.

Over the years, Herndon was in and out of the hospital. He lost the ability to walk multiple times, gaining it back to some degree thanks to physical therapy and medications until a relapse last fall left him in a wheelchair.

While many patients with extraordinarily rare diseases now find others like themselves thanks to genetic testing being cheaper and more widely available, Herndon never did. He found some companionship in the deaf community and among others with muscular disorders, but told NBC News in May that he would have loved to meet someone who could relate to the ups and downs of his particular disease.

If I knew someone who was 50 years old and had the same thing, if they were doing amazing, that would clear up a lot of anxiety."

If I knew someone who was 50 years old and had the same thing, if they were doing amazing, that would clear up a lot of anxiety, Herndon said at the time. If we found out this is progressive, that would suck, but at least I would know what to expect.

Despite the unique challenges Herndon faced, he kept a positive outlook often using humor to lighten the mood during his lengthy hospital stays, spending as much time as he could with his siblings, Maxwell, 17, and Miranda, 11, and when he was well enough attending St. Louis University where he enjoyed studying political science and theology.

Researchers knew Herndon's condition was going to get worse, but they were not sure how quickly he might decline. Then they stumbled upon something that they believed could stop the progression and possibly save his life.

Dr. Hugo Bellen, an investigator with the Howard Hughes Medical Institute and a professor at Baylor College of Medicine who studies genetics and neurobiology, was studying Herndon's mutation in fruit flies. Bellen discovered that a powerful antioxidant, NAC-Amide, showed promising results in stopping the disease's decline. But the medication was not approved by the Food and Drug Administration for use in patients yet.

Bucelli, Herndon's neurologist, worked tirelessly with the FDA to establish a protocol for the medication that would have been considered safe to try on Herndon. As Herndon worsened during his most recent hospital stay, eventually becoming unresponsive and going on life support, the FDA finally granted approval for Herndon to try it barely an hour after an MRI showed the disease had spread to his brain.

With irreversible brain damage, it was too late to try the drug. Herndons family made the painful decision to remove him from life support something Herndon had expressed to them that he wanted should he ever get to that point. The following day, held by his father, mother and brother, Herndon died, his mother, Michele Herndon, said.

While the drug approval came too late for Herndon, doctors have identified another patient who appears to have the same type of mutation as him: a young child in Ohio. Bucelli said he is sending the research he did on Herndon to the physicians in Ohio, which should open the door for them be able to receive the drug for their patient.

"Mitchell could potentially have a direct impact on this next patient."

"Mitchell could potentially have a direct impact on this next patient," Bucelli said.

In the meantime, Bellen has submitted the first-ever paper on Herndon's particular mutation for publication in a scientific journal. He said he suspects there are more patients who will be discovered to have the condition, and in the paper, Bellen proposed a name for it: Mitchell Disease.

Herndon's parents said their son was always eager to help medical professionals, whether it was letting students practice taking medical histories on him or allowing newer nurses to do procedures on him, even if there were more experienced nurses available. His mother said she hoped helping to find cures for this condition as well as others will be part of her son's legacy.

"Our decision to donate his body was just another way that we know he will continue to advance medical research and hopefully pave the way for future patients with his genetic mutation," Michele Herndon told NBC News via email. "We always knew that he believed his body was just that a body. And his soul is what would live on."

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This teen had a disease so rare, it didn't have a name. His legacy could help countless others - NBC News