Status of Proteins Housing DNA Controls How Cells Maintain their Identity – PRNewswire

NEW YORK, Oct. 31, 2019 /PRNewswire/ -- The inheritance, not only of DNA, but of changes to proteins that package it, maintains the identity of cells as they multiply, a new study finds.

Led by researchers at the NYU School of Medicine, the study sheds light on the process by which each cell transmits its identity to the next cellular generation as it multiplies by dividing in two during development. All cells have the same, complete set of DNA, but each is programmed to activate or silence certain genes, determining whether they become, for instance, heart cells instead of intestinal cells, researchers say.

Published online on October 31 in Cell, the new study confirms that mechanisms preserving cell identity are based on how DNA is packaged. With the nuclei of cells, chains of molecular DNA are known to be wrapped around sets of proteins called histones in repeating units called nucleosomes, all within the larger superstructure called chromatin.

Further, the "tails" of the histones are known to extend outside of this wrapping, making them available for chemical changes that determine whether a chromatin region is "open," with the DNA accessible, ortightly compacted, with the genes residing there silenced. The current study authors devised a method to track whether chemical modifications to histones in nucleosomes were accurately passed from a parent cell to the same DNA regions in the two cells it forms upon division.

"Based on our new method, experiments suggested that compaction based on histone modifications at key positions is a fundamental feature of inheritance in cells, with the related silencing passed on to keep genes from being expressed in the wrong context," says study first author Thelma Escobar, PhD, a postdoctoral scholar in the Department of Biochemistry and Molecular Pharmacology at NYU School of Medicine.

Mapping Inherited Nucleosome Changes

The research team developed a system in which "old" nucleosomes, those positioned throughout a parent cell's DNA, could be tagged before the DNA was copied as a prerequisite to cell division.

Researchers then used the specificity of the CRISPR-Cas9 gene editing system to attach a molecule called biotin but only to those nucleosomes present within a single gene of their choice. That in turn let them follow the fate of these marked nucleosomes in genes known to occur in either open or silent chromatin as the cell copied its DNA.

The new method revealed that only the nucleosomes from silent, compacted chromatin were inherited ending up at the same locale on the newly replicated DNA as they were in the parent DNA. The nucleosomes from the open chromatin were not inherited, and were distributed widely throughout the newly copied chromatin.

Based on their experiments, the authors argue that chemical modifications to histones that foster chromatin compaction are inherited as a fundamental property preserving a cell's identity. Open chromatin, on the other hand, did not rely on this "positional inheritance," as its DNA can be activated as needed by regulatory proteins that interacted with the DNA directly.

Furthermore, the research team found that only within compacted, silent chromatin could the proteins responsible for chemically modifying histone tails recognize ("read") modifications in parental nucleosomes and then duplicate ("write") them on newly forming nucleosomes.

The study also suggests that histones forming nucleosomes in silent chromatin may be escorted to the proper place in replicating DNA by novel chaperone proteins, which the researchers are currently seeking to identify.

"Strikingly, it may be through gene repression that histone modifications show a heritable gene regulatory system not present in more primitive cells like bacteria, potentially playing a role in the greater complexity of human cells," says senior study author Danny Reinberg, PhD, the Terry and Mel Karmazin Professor of Biochemistry and Molecular Pharmacology at NYU Langone Health. "At the same time, cancer arises in some cases from this very complexity as cells that randomly lose compaction due to a loss of histone chemical modifications see their usually silenced genes become active."

"In this way, cancer cells evolve to overcome treatments or limits on their growth, and we hope the current work will suggest new ways to stop this," says Reinberg, also an investigator with the Howard Hughes Medical Institute.

Along with Escobar and Reinberg, study authors from NYU Langone School of Medicine were Ozgur Oksuz, Ricardo Saldaa-Meyer, Nicolas Descostes, and Roberto Bonasio. Funding for the work was provided by the Howard Hughes Medical Institute and the National Cancer Institute grants 9R01CA199652-13A1, 3R01CA199652-14S1, and P30CA016087.

Contact: Gregory Williams, 212-404-3500, gregory.williams@nyumc.org

SOURCE NYU School of Medicine

https://med.nyu.edu/

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Status of Proteins Housing DNA Controls How Cells Maintain their Identity - PRNewswire

Opportunities and Challenges in Cell and Gene Therapy Development – Genetic Engineering & Biotechnology News

Ger Brophy, PhDExecutive Vice PresidentBiopharma ProductionAvantor

Genuine progress is being made in the longstanding battle to effectively treat and control cancer. The National Cancer Institute projects that nearly five million more U.S. citizens are expected to survive cancer in 2029 than in 2019.1 Therapeutic tools such as next-generation sequencing and advances in immunotherapy are just two ways that fundamental scientific breakthroughs and innovative thinking are realizing the potential for new cancer treatments.

One of the most revolutionary breakthroughs in this new era is cell and gene therapy. At its most basic definition, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patients cells as a drug to treat disease. According to a paper published in the Journal of Gene Medicine, somewhere around 2600 gene therapy clinical trials had been undertaken in 38 countries around the world as of November 2017.2

These clinical trials demonstrate that the recent attention being paid to gene and cell therapy is not just hype. Some have noted that a select number of approved cell and gene therapies are for relatively small patient groups. However, its exciting to see the number of trials grow, especially when one considers this technologys ability to impact patients lives.

Its true that the number of patients receiving treatment is relatively small compared to other therapeutic regimens, but thats to be expected. Many of the biopharmaceutical researchers and manufacturers started with smaller, defined patient populations and, in particular, those with pediatric relapse refractory acute lymphoblastic leukemia. In part, these early efforts were directed at this type of cancer because the researchers wanted to deal with small populations that they understood well and, in many cases, had few or no other options for treatments.

The success of these initial efforts has led to broader programs targeting larger populationsstarting with leukemia and lymphoma. Ultimately, the most challenging opportunityand the one with the greatest potential for beneficial outcomesis multiple myeloma. If these patients begin to see benefits from cell and gene therapies, it will justify the incremental approach the industry has been taking.

The genuine, almost unprecedented potential for cell and gene therapy cannot be understated. For the first time, people are talking about curing these ruthless, relentless diseases. In a way never before possible, were taking control of and harnessing the patients own immune system to fight these cancers. Among the first patients treated for acute lymphoblastic leukemia, several are alive and thrivingfour, five, and six years later.

The game changer here is that cell and gene therapy uses the bodys own systems, either the cellular immune system or the ability to repair and replace defective or missing genes. CAR T-cell therapy is arguably among the most personalized medicines one can consider. The patients own T cells are extracted, modified, activated, expanded, purified, and returned to the patient.

Significant growth is underway in the size and sophistication of companies and organizations entering the cell and gene therapy markets. Many of the early movers in cell and gene therapy were small biotech startups. In some cases, their treatments were supported by major hospital centers.

Increasingly, weve all seen a greater interest from the major biopharma companies. Novartis was probably the biggest; it started earliest and was successful in getting approval for Kymriah. Since last year, weve seen several important acquisitions by Gilead and Bristol-Myers Squibb, and major biopharma companies are participating in large strategic partnerships in China. As companies of this size get involved, the hope is that they will leverage their increased breadth and depth to develop novel products, instigate new trials, and find ways to manufacture therapies at scale.

If the cell and gene therapy industry is to succeed, it must overcome challenges of two kinds: scalability and manufacturability. These challenges may be summarized in a set of questions: Can we manufacture cell and gene therapies at scale? If we can manufacture these treatments at scale, then can we do so safely? Can we do so at a reasonable cost so the populations that are affected by these diseases can access treatments?

With cell therapy, the single biggest point of variability is the patients own cells. By their very nature, these cells are individual to the patient, and their health implications for the patient should be considered as an integral part of cell processingat least as far back as the time of leukapheresis.

Variables and failure modes must be taken out of cell processing systems. We can standardize and miniaturize these systems, and we can enclose them so that theyre not exposed to failure modes. Also, we can improve technologies, like sterile fluid transfer, if we use excipient technology to further stabilize production. Finally, we can use analytical technology to understand the factors that contribute to a therapys success or failure.

Cell therapy producers and the companies that support and supply them need to become more innovative. In areas such as cell culture components, production chemicals, single-use technologies, sterile fluid transfer, and excipientsand the technology surrounding those process componentsthere is value to improving collaboration and trying new solutions to address the issues of manufacturability and scale.

We need to better analyze and understand the variability that comes from the research data, even at the early stages of these trials, and use it to correlate with clinical and process outcomes. Taking out manual steps as early as possible is important, as well as creating closed systems using sterile fluid transfer technologies.

One of the most significant challenges is finding solutions around side effects. As we understand how to provide a more efficacious dose, perhaps using fewer cells, some of the side effects of these drug therapies may improve. Furthermore, we must find scalable ways to reduce costs.

Ultimately, these drugs must be developed in a more cost-effective manner. Thats an area where technology providers and suppliers can play a significant role, by closing and automating systems and by understanding the contribution of labor and overhead and possible economies of scale from reducing processes.

There have been encouraging improvements in the way various regulatory groups have supported gene and cell therapy. To a certain degree, groups representing different regionsNorth America, Europe, and Asiahad been perceived to be setting precedents independently. More recently, it appears that regulatory bodies have been very open and collaborative in acknowledging that cell and gene therapies differ from more mature treatments such as biopharma drugs for cancer. The regulatory bodies have shown that they are willing to put the appropriate regulatory system into place to streamline the approval process and institute the ongoing monitoring of cell and gene therapies.

The U.S. FDAs support on CAR T-cell technologies is a good example. Regulators are allowing flexibility in the normal hierarchy of how clinical trials are performed, particularly in Phase II and III trials, but the companies must still address the FDAs postmarketing comments and safety issues.

Some have suggested that, ultimately, almost all cancer treatments will be based on gene and cell therapy approaches since they represent the most personalized form of treatment, which is, theoretically, the one with the highest potential for success.

Thats probably overly ambitious. Both large molecules and small molecules will continue to provide trusted, effective solutions with each type of drug product finding its niche. For example, large molecules are being developed for areas like neurodegeneration and are still offering great potential.

Its worth remembering that monoclonal-based therapies and biopharmaceuticals have really only started to make a significant impact in the last 15 to 20 years. Cell and gene therapies are just starting and have yet to make a significant market impact. But considerable effort is going into developing, understanding, and characterizing drug targets, as well as the development of technology to make targeted drugs in production-level volumes.

All these developments are exciting and offer a great deal of hope. It is clear that gene and cell therapies work and save lives. The challenge now is to scale their production. It is also clear that cell and gene therapies can emulate other therapeutic approaches that have transitioned from theoretical possibility to practical reality. As a similar transition occurs for cell and gene therapies, the production issues that need to be addressed will be seen more clearly, prompting action that will bring us to the next stage of development.

References1. Bluethmann SM, Mariotto AB, Rowland, JH. Anticipating the Silver Tsunami: Prevalence Trajectories and Comorbidity Burden among Older Cancer Survivors in the United States. Cancer Epidemiol. Biomarkers Prev. 2016; 25: 10291036.2. Ginn SL, Amaya AK, Alexander IE, et al. Gene therapy clinical trials worldwide to 2017: An update. J. Gene Med. 2018; 20(5): e3015.

Ger Brophy, PhD, is Executive Vice President, Biopharma Production at Avantor

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Tmunity Raises $75 Million in Series B Financing to Advance Next-Generation T-Cell Therapies – Business Wire

PHILADELPHIA--(BUSINESS WIRE)--Tmunity Therapeutics, in pursuit of its vision to save and improve lives by delivering the full potential of next-generation T-cell immunotherapy, closed a $75 million Series B financing. The financing was led by Andreessen Horowitz (also known as "a16z"), a venture capital firm that backs bold entrepreneurs building the future through technology and includes participation from a16zs Cultural Leadership Fund. Joining the Series B financing are Westlake Village BioPartners, Gilead Sciences, The University of Pennsylvania, Be The Match BioTherapies and BrightEdge, the philanthropic impact fund of the American Cancer Society.

The proceeds from the Series B will continue to fund ongoing and planned research, clinical development of product candidates, the continued build-out of the Companys proprietary, vertically-integrated viral vector and cell therapy product manufacturing, working capital and other general purposes. Since inception, Tmunity has raised $231 million.

We are fortunate to be funded by impressive investors who share our commitment to patients and our vision to dramatically change the way cancer is treated, said Usman Oz Azam, MD, President and Chief Executive Officer of Tmunity. We see ourselves leading the innovation of the future of oncology treatment by uniting our foundational competences in cell therapy with expertise in building new constructs, translating them and getting them into the clinic.

As part of the Series B financing, Jorge Conde, General Partner at a16z, will join the Companys Board of Directors. Mr. Conde leads a16zs investments that are at the cross section of biology, computer science and engineering.

"To win the war on cancer, we need smarter weapons. Tmunitys founders Carl June and Bruce Levine invented CAR-T, one of the most profound breakthroughs against cancer in recent history. Together with Oz Azam, who with his team, brought the first CAR-T therapy to market, the company has built a pioneering platform that has produced an unrivaled therapeutic pipeline with programs already in human clinical trials for both solid and liquid tumors. This is the dream team to deliver on the bold and promising mission to cure disease using engineered T-cells," said Conde.

About Tmunity Therapeutics

Tmunity is a private clinical-stage biotherapeutics company focused on saving and improving lives by delivering the full potential of next-generation T-cell immunotherapy to patients with devastating diseases. Integrating a foundational collaboration with the University of Pennsylvania (Penn) with the groundbreaking scientific, clinical, and manufacturing expertise, and the demonstrated track record of its founders (Carl June, MD; Bruce Blazar, MD; Bruce Levine, PhD; Yangbing Zhao, MD, PhD; Jim Riley, PhD; and Anne Chew, PhD), Tmunity represents a new center of gravity in translational T-cell medicine. Through the University of Pennsylvania, the Parker Institute for Cancer Immunotherapy and collaborations with the University of California San Francisco and Childrens Hospital of Philadelphia, the company is developing a diversified portfolio of novel treatments that exhibit best-in-class control over T-cell activation and direction in the body, with a focus in cancer and three programs currently in clinic development. With headquarters in Philadelphia, Tmunity utilizes laboratories and production facilities at Penn and its own dedicated cGMP manufacturing facility in East Norriton, PA, to pursue process improvement and production scale-up in support of clinical development of its T-cell therapies. For more information, visit http://www.tmunity.com and connect with us on social media at @TmunityTx and LinkedIn.

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Tmunity Raises $75 Million in Series B Financing to Advance Next-Generation T-Cell Therapies - Business Wire

Beam Therapeutics Announces Collaboration and Exclusive License Agreement with Prime Medicine for Prime Editing Technology – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Beam Therapeutics, a biotechnology company developing precision genetic medicines through base editing, today announced that it has entered into a collaboration and license agreement with a newly-formed company, Prime Medicine, Inc. to research and develop a novel gene editing technology called prime editing, recently developed by one of Beams co-founders, David Liu, Ph.D., and his group at the Broad Institute of Harvard and MIT.

Under the agreement, Beam has the exclusive right to develop prime editing technology for the creation or correction of any single-base transition mutations, as well as for the treatment of sickle cell disease, both of which Beam is already pursuing with its base editing technology. Transition mutations (e.g. A to G, C to T) are the largest single class of disease-associated genetic mutations, and are also potentially treatable with base editing. Beam plans to evaluate prime editing technology for potential use in future programs.

Part of Beams strategy is to continue to access emerging technologies in gene editing and delivery, while finding new ways to create meaningful options for patients. Our collaboration with, and contribution to the formation of, Prime Medicine is a great example of that approach, allowing us to incorporate prime editing into the Beam platform, said John Evans, chief executive officer of Beam. This partnership enables both companies to advance the technology in distinct spaces, with Beam focusing on the kinds of edits that are most similar to our base editing technology.

As part of the collaboration, Beam is providing initial interim leadership to Prime Medicine for the first year of the collaboration, and will have the right to designate a member on Prime Medicines board. The parties will also grant each other non-exclusive licenses to certain CRISPR technology and delivery technology to enable the development of prime editing products.

About Beam Therapeutics

Beam Therapeutics is developing precision genetic medicines through base editing. Founded by leading scientists in CRISPR gene editing, Beam is pursuing therapies for serious diseases using its proprietary base editing technology, which can make precise edits to single base pairs in DNA and RNA. Beam is headquartered in Cambridge, Massachusetts. For additional information, visit http://www.BeamTx.com.

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Beam Therapeutics Announces Collaboration and Exclusive License Agreement with Prime Medicine for Prime Editing Technology - Business Wire

Editas Medicine In The Realm Of Designer Humans – Seeking Alpha

Comparison is the essential valuation activity

Readers familiar with our work may want to skip to the "Comparing Details" section below.

Advances in Genome understanding and prospective adjustments continue at a startling pace. Equity investments provide a means of maintaining perspective and other SA contributors help with the industry development details.

This article rewards investors who choose to direct their investments of TIME and capital to those alternatives with the highest likelihood of successful rates of return among ones compared under identical important measures.

Now, Editas Medicine (EDIT) provides attractive answers to these questions:

These are questions often neither asked nor answered by many investment analysis reports. The commonplace approach is to present those aspects of one investment which may set it apart from others, but fail to make the essential decision-supporting step of comparing alternatives on an equal-measure basis.

Instead of limiting a value-search to industry competitors, our focus is on the alternatives which may address the investor's objectives of his investing mission, not necessarily of a stock candidate's competitive industry concerns.

To that end we turn to an information expert on what is currently of importance to investors - YAHOO Finance - and what also diverts the attention of investors initially interested in the stock of Editas Medicine. From its website traffic records Yahoo lists five other stocks "People also watch." They are NTLA, SGMO, BLUE, ONCE, and CLLS.

With the alternative investment choices in hand, we then turn to folks involved every market day with making bets (usually big bets) about how far their prices are likely to get pushed - both up and down. Those price limits are defined in the choices they make in the way they will protect their capital which must be exposed to market risk as they conduct their every-day market-making activities in large-volume "block trade" transactions.

Price range forecasts are being made in separate hedging deals over time periods defined by the contract lives of the derivative securities involved. Those judgments contain the updated "fundamentals" of interest to all evaluators, collected 24x7 by armies of market-maker (MM) employees world-wide.

Such forecasts are constantly being refined every moment investment markets are operating, and are made part of every market-day's closing records. They provide an historical record (in subsequent market price actions) of how well the "smart money" can make useful forecasts - for specific stocks, ETFs, and indexes.

Present-day markets are driven by major investing organizations commanding multi-billion dollar portfolios with stock contents which can only be adjusted by negotiated volume (block) trades between peers, not by "open auction". Such trades set and move posted prices.

The individual investor typically is merely along for the ride. He/she needs to have a sense of where the negotiators are likely to head, pricewise. Conventional analysis often provides superficial descriptions and little linkage between operating minutia and price forecasts. As an example here is how Yahoo Finance reports on EDIT.

Editas Medicine, Inc. operates as a clinical stage genome editing company. The company focuses on developing transformative genomic medicines to treat a range of serious diseases. It develops a proprietary genome editing platform based on CRISPR technology to target genetically addressable diseases and therapeutic areas. The company develops EDIT-101 for Leber Congenital Amaurosis type 10, a genetic form of vision loss that leads to blindness in childhood. It also develops other therapies for eye diseases, such as Usher Syndrome 2A, which is a form of retinitis pigmentosa that also includes hearing loss; Retinitis Pigmentosa, a progressive form of retinal degeneration; and Herpes Simplex Virus 1 that causes lifelong infections leading to ocular and oral disease.

In addition, the company develops hematopoietic stem cells for treating sickle cell disease and beta thalassemia. It has a research collaboration with Juno Therapeutics, Inc. to develop engineered T cells for cancer; strategic alliance and option agreement with Allergan Pharmaceuticals International Limited to discover, develop, and commercialize new gene editing medicines for a range of ocular disorders; and strategic research collaboration and cross-licensing agreement with BlueRock Therapeutics to combine their respective genome editing and cell therapy technologies to discover, develop, and manufacture engineered cell medicines. The company also has a strategic research collaboration agreement with Editas Medicine, Inc. to explore in vivo delivery of genome editing medicines to treat neurological diseases. The company was formerly known as Gengine, Inc. and changed its name to Editas Medicine, Inc. in November 2013. Editas Medicine, Inc. was founded in 2013 and is headquartered in Cambridge, Massachusetts.

Not much help, is it?

Instead, here is what the MMs' hedging actions tell today about how high (and low) the stocks might get priced, and how they each behaved subsequent to prior forecasts like the ones now being seen:

Figure 1

The essence of valuation is in comparison, which requires that the compared measures be as close to identical as possible. To that end we place all of our valuations in a carefully defined set of measures, and describe them in as parallel set of comparisons as is possible.

To do so often presents what many readers recognize as text and ideas they have encountered before, as they have in our just-published comparison between Microsoft and Boeing. The use of the heading for this section of the article as an accelerant to reading provides for experienced readers an economy of time and effort, while leaving for the newly-initiated the opportunity for an important introduction.

What is important to us in this analysis is how big a price gain is in prospect, column [E], and how likely is today's RI forecast to produce a profit [H] as a proportion of the [L] sample of such forecasts. That combination result appears in the [I] %payoff which includes loser forecasts as well as the 82% winners. The size of [I] relative to [E] is a measure of [E]'s credibility in [N].

Time required [J] to accomplish the payoff is another important dimension for any investment mission. The retirement, tuition, or health emergency clock won't patiently wait for "long-term-trend" investments to be "sure" (like EK, GM, GE, and others) of their "passive investment" buy&hold strategy results. Compound Annual Gain Rates (CAGR) are the essential measures [K]. Figure 3's rows are ranked by the historical results (of today's RI) statistic.

One additional complication of being time-efficient in an investment strategy is that the score-keeping can't be easily sliced up into uniform time periods. That is not what happens to holdings in an active investment strategy. Gains (and losses) occur in irregular lumps of time, and we need to evaluate likely prospects in the way they may be accumulated.

What is done in proper financial analysis of any capital commitment is to anticipate the RATE of gain or cost in units of change per time of involvement. The most commonly used measure is basis points per day, where a basis point is 1/100th of a percent.

That's a tiny unit, but is what works best. Put together and maintained each day for a year, 19 of them would double your investment. They can be powerful.

In Figure 1 we use the Odds of gain [H] as a weight for the average prior payoffs [I], and take the complement of [H] ( 100 - H ) as a weight for the risk prospect [F]. Put together as [O] + [P] in [Q] we have an odds-weighted net outcome of each row's prior MM RI forecast sample [L]. Then by converting those [Q] nets into bp/day in [R] we have a guide to making investment selection decisions across a broader array of alternatives.

Taking measurements into such precision where the potentials are great for errors in forecasting may only serve to point out the limits of their usefulness. And where the differences between alternatives are great, the efforts involved may not be practical. But the fact remains that investors and investment organizations are determined to risk capital in these uncertain ventures, and progress in some areas of the unknown need guide-rails.

So figure 1 may tell us that if the future is repeated then in this case EDIT is a superior portfolio choice to any of the five alternatives generally being considered by investors consulting Yahoo Finance's data. EDIT's stock superiority lies principally in that in the next 3 months it has better odds of seeing a price +19% higher while encountering interim price drawdowns not significantly worse than any of the alternative stock investments, and do it in approximately the next 8 weeks.

That rate of gain is a CAGR of +201%, which compares to a probable parallel investment in the S&P 500 index ETF (SPY) of some +15%. Out of a population of over 2,700 other coming price range forecasts from the same source an average CAGR of +17% involves roughly equal interim risk exposure of -10% which is typically not only encountered, but also suffered in terms of actual capital loss experience, reducing that forecast population's expected +14% gain to only +3% in the process.

Meanwhile, the best 20 candidate stock investments from that population actually achieved +19% gains, better than the +14% expected, and by being alert to day-by-day price moves accomplished them in the same 8 week average holding period of EDIT, for CAGR rewards at a 342% rate.

Will all these price changes be repeated? Probably not precisely, but at least you have some norms to compare with.

To provide a sense of how EDIT price range forecasts by MMs have been trending recently Figure 2 shows daily expectations for the past 6 months and Figure 3 shows once-a-week excerpts over the past two years.

Figure 2

The small blue picture here shows the distribution of forecast Range Indexes during the past 5 years' 1261 market days. Recording the daily balance between expected upside and downside price changes likely, the current measure of 29 is clearly below its visual average, supporting the 82/100 odds of higher coming prices.

Figure 3

Editas Medicine presents evidences of coming price change prospects which are superior to many relevant equity investment alternatives, and justify its buy as a near-term wealth-building investment.

Disclosure: I/we have no positions in any stocks mentioned, but may initiate a long position in EDIT over the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Peter Way and generations of the Way Family are long-term providers of perspective information, earlier helping professional investors and now individual investors, discriminate between wealth-building opportunities in individual stocks and ETFs. We do not manage money for others outside of the family but do provide pro bono consulting for a limited number of not-for-profit organizations.

We firmly believe investors need to maintain skin in their game by actively initiating commitment choices of capital and time investments in their personal portfolios. So, our information presents for D-I-Y investor guidance what the arguably best-informed professional investors are thinking. Their insights, revealed through their own self-protective hedging actions, tell what they believe is most likely to happen to the prices of specific issues in coming weeks and months. Evidences of how such prior forecasts have worked out are routinely provided in the SA blog of my name.

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Editas Medicine In The Realm Of Designer Humans - Seeking Alpha

Hemanext Announces CE Mark Submission for the HEMANEXT ONE Red Blood Cell Processing System – Benzinga

Regulatory filing is a major step toward commercialization of transfusion-medicine innovation

LEXINGTON, Mass. (PRWEB) November 01, 2019

Hemanext Inc., a privately held medical technology company dedicated to improving patient outcomes through fewer and better red blood cell (RBC) transfusions, today announced CE Mark submission for HEMANEXT ONE, the company's initial product offering that is designed to provide a higher-quality blood product for transfusion patients.

The HEMANEXT ONE processing system reduces the fuel for oxidative damage prior to and during storage, and converts a unit of conventional, leukoreduced RBC into a transfusion-ready unit of HEMANEXT ONE RBC.

"We have seen a growing body of scientific evidence that oxidative damage to RBCs could have a negative impact on clinical outcomes for many acute and chronic patient populations that require large volumes of transfusions," said Paul M. Ness, MD, Senior Director, Division of Transfusion Medicine and Professor of Pathology, Johns Hopkins University School of Medicine; Editor, Transfusion, the peer-reviewed journal of the American Association of Blood Banks (AABB) (2003-2018); Past President, AABB. "Improving the quality of RBCs could enhance patient care and simultaneously reduce the quantity of RBC units required to treat many diseases and conditions."

Hemanext anticipates receiving CE Mark approval in the first half of 2020, with commercialization initiatives for the HEMANEXT ONE system in Europe commencing in the second half of the year. Hemanext also expects to submit a 510(k) premarket notification to the U.S. Food and Drug Administration (FDA) in 2020.

"Our CE Mark submission is a significant milestone for Hemanext. It is the culmination of years of research and collaborations with the transfusion medicine community in Europe," said Hemanext President and CEO Martin Cannon. "We are grateful for the partnerships that have brought us another step closer to creating a world with fewer and better transfusions."

ABOUT HEMANEXT

Hemanext is a privately held medical technology company dedicated to improving the quality, safety, efficacy and cost of transfusion therapy. The company's research and development efforts center on the study and future commercialization of hypoxically stored red blood cells (RBCs). HEMANEXT ONE, our initial product offering, is designed to improve the quality of life for chronic and high-volume acute transfusion patients while reducing costs.

Visit Hemanext.com to learn more.

Dr. Ness serves as a clinical advisor to Hemanext.

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Co-Administration Of iRGD Enhances Tumor-Targeted Delivery And Anti-Tu | IJN – Dove Medical Press

Yi Zhong,1,* Tao Su,1,* Qiuxiao Shi,1 Yanru Feng,1 Ze Tao,1 Qiuxia Huang,1 Lan Li,1 Liqiang Hu,1 Shengfu Li,1 Hong Tan,2 Shan Liu,3 Hao Yang1

1Key Lab of Transplant Engineering and Immunology, MOH, West China-Washington Mitochondria and Metabolism Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China; 2Department of General Surgery, Chengdu Integrated TCM & Western Medicine Hospital (Chengdu First Peoples Hospital), Chengdu 610041, Peoples Republic of China; 3Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial Peoples Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Shan LiuDepartment of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial Peoples Hospital, No. 32, West Second Section First Ring Road, Chengdu, Sichuan 610072, Peoples Republic of ChinaTel +86 28 6138 2518Email shanliusyy@163.comHao YangKey Lab of Transplant Engineering and Immunology, MOH, West China Hospital, No. 1, Keyuan 4th Road, Hi-tech Zone, Chengdu 610041, Peoples Republic of ChinaTel +86 28 85164031Email yanghao@scu.edu.cn

Background: Nanoparticles exhibit great promise for improving the solubility and tissue-specific distribution of chemotherapeutic agents; however, the passive and highly variable enhanced permeability and retention (EPR) effects observed in tumors frequently leads to insufficient delivery of nanodrugs into tumors. The tumor-penetrating peptide iRGD can actively enhance tumor-selective delivery of nanoparticles into tumors by binding to integrin and interacting with tissue-penetrating receptor neuropilin-1.Materials and methods: To improve colorectal cancer treatment, in this study, we prepared a paclitaxel (PTX)-loaded PLGA nanoparticle (PLGA-PTX) and evaluated its tumor-targeting and antitumor activity by co-administration with iRGD.Results: Compared to free PTX, encapsulated PTX retained preferential cytotoxicity toward various colorectal cancer cells while effectively sparing healthy cells. PLGA-PTX treatment resulted in cell cycle arrest at the G2/M phase and apoptosis, leading to inhibition of cancer cell migration and invasion. PLGA-PTX combined with iRGD displayed little enhancement of cytotoxicity in vitro. Despite this, iRGD receptors integrin and neuropilin-1 were found to be primarily overexpressed on abundant tumor vessels in mice bearing colorectal tumors. Consequently, co-administration of nanoparticles with iRGD promoted the selective delivery of nanoparticles into tumor tissues in vivo. Additionally, the combined regimen enhanced the antitumor effects compared to those of each individual reagent.Conclusion: Our findings suggest that PLGA nanoparticles combined with the iRGD peptide provide a promising drug delivery strategy for facilitating active drug accumulation into tumors, given that iRGD receptors are overexpressed on tumor vessels. This co-administration system lacking covalent conjugation provides a more convenient means to combine various therapeutic agents with iRGD to achieve personalized nanotherapy.

Keywords: tumor penetrating peptide, nanoparticle, iRGD, paclitaxel, tumor vasculature, colorectal cancer

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Co-Administration Of iRGD Enhances Tumor-Targeted Delivery And Anti-Tu | IJN - Dove Medical Press

Severe Vision Loss From Niacin (Vitamin B3) Can Be Reversed – SciTechDaily

In a first-of-its-kind clinical report, retina specialists at the New York Eye and Ear Infirmary of Mount Sinai (NYEE) have shown that severe vision loss from a self-prescribed high dose of over-the-counter niacin is linked to injury of a specific cell type in a patients eye. The experts report that discontinuing the vitamin led to reversal of the condition and have published their findings in the fall issue of Journal of VitreoRetinal Diseases.

Niacin, also known as vitamin B3, is used for lowering hyperlipidemia or cholesterol and comes in prescription and over-the-counter forms; it can produce a rare toxic reaction called niacin-induced cystoid maculopathy, a form of retinal swelling.

Just because nutritional supplements are available without prescription does not mean they are completely safe to use without supervision. Jessica Lee, MD

People often live by the philosophy that if a little bit is good, more should be better. This study shows how dangerous large doses of a commonly used over-the-counter medication can be, said lead investigator Richard Rosen, MD, Chief of Retina Services at NYEE and the Mount Sinai Health System. People who depend on vision for their livelihood need to realize there could be long-lasting consequences from inadvertent overdosing on this vitamin.

This case serves to remind everyone about the importance of talking to ones physician prior to taking any supplement, or over-the-counter product. Just because nutritional supplements are available without prescription does not mean they are completely safe to use without supervision, explains corresponding author Jessica Lee, MD, Assistant Professor of Ophthalmology at the Icahn School of Medicine at Mount Sinai. No matter how benign a supplement or over-the-counter product may seem, the correct dosage and potential interactions with other medications should be carefully reviewed with a doctor, to avoid preventable unexpected consequences. This case illustrates how dangerous casual self-prescribing of megadoses of vitamins can be.

Sufficient niacin, also called vitamin B3, is important for general good health. However, like many nutrients, too much can be damaging to the human body. To be effective in reducing cholesterol, high doses are needed, which can pose health risks including vision problems, liver damage, glucose intolerance, and gastrointestinal problems.

The team of investigators from NYEE reported on a 61-year-old patient who arrived at the hospital with worsening blurry vision in both eyes that began a month earlier. The initial exam showed that the patient was almost legally blind, with best-corrected visual acuity of 20/150 in the right eye and 20/100 in the left eye. The patient told doctors his medical history included significant hypertension and hyperlipidemia, but initially failed to disclose the extent of his self-prescribing. Subsequently, he admitted to taking an extensive list of supplements, which included three to six grams of niacin daily for several months to reduce his risk of cardiovascular events and was unaware of the risk to his eyesight. He purchased the supplement at a drug store after a doctor told him he had high cholesterol. The standard dosage is one to three grams a day with a maximum dose of six grams, but doctors typically warn against treating the condition with supplements purchased over the counter and prefer to prescribe and monitor an FDA-approved dose of niacin.

While retina specialists have been aware of this unusual reaction to niacin for many years, such a textbook example of extreme toxicity and recovery has never been as well documented by imaging and functional testing. Richard Rosen, MD

NYEE clinicians diagnosed the problem using several state-of-the-art technologies, including fluorescein angiography, optical coherence tomography (OCT), and multifocal electroretinography (MERG), to examine his retina for evidence of cellular damage and monitor his response to therapy. Fluorescein angiography uses fluorescent dye to trace blood flow through retinal arteries and veins, looking for leaks. OCT is an advanced structural imaging technique that reveals the cross-sectional details of the retina cells, layer by layer. MERG measures the electrical signals from different layers of cells in the eyes.

The imaging allowed investigators to diagnose a rare toxic reaction called niacin-induced maculopathy. The high dose of niacin led to cystoid macular edema of the retina, which is fluid in the macula (a small area in the center of the retina that produces detailed and centralized vision) that causes swelling. The technology also allowed investigators to identify the cellular structures responsible for the patients condition. The MERG recorded in this case showed reduced b-waves, which indicated that cells affected by the toxicity were the Muller cells, which span the depth of the retina like support columns.

Discontinuation of the vitamin reversed this effect and restored retinal function and electrical signals. This led investigators to demonstrate, for the first time, that the Muller cells were the target of niacin toxicity, and the cause of niacin maculopathy.

This case illustrates how dangerous casual self-prescribing of megadoses of vitamins can be. Jessica Lee, MD

Ophthalmologists from NYEE explained the situation to the patient and advised him to stop taking the over-the-counter niacin immediately. At his one-week follow-up appointment, his vision had noticeably improved. Two months later, the dysfunction had completely resolved and his vision was back to 20/20. Through the high-tech structural and metabolic imaging, researchers observed that the patients Muller cells had gradually yet dramatically recovered.

While retina specialists have been aware of this unusual reaction to niacin for many years, such a textbook example of extreme toxicity and recovery has never been as well documented by imaging and functional testing, said Dr. Rosen.

In this instance the patient was particularly fortunate that the physicians who saw him were alert to the possible cause and were able to confirm their diagnostic suspicions with appropriate testing. This may not always be the case and other patients may not have such a successful outcome, added Dr. Lee.

Reference: Optical Coherence Tomography, Fluorescein Angiography, and Electroretinography Features of Niacin Maculopathy: New Insight Into Pathogenesis by Jessica G. Lee, MD, Anu Patel, MD, Alessandra Bertolucci, MD and Richard B. Rosen, MD, 1 October 2019, Journal of VitreoRetinal Diseases.DOI: 10.1177/2474126419877567

Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It has the formula C6H5NO2 and belongs to the group of the pyridinecarboxylic acid.

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Severe Vision Loss From Niacin (Vitamin B3) Can Be Reversed - SciTechDaily

ACS 2019: Outcomes in Renal Cell Carcinoma (RCC) Patients Undergoing Inferior Vena Cava (IVC) Ligation versus Thrombectomy: A Retrospective,…

San Francisco, California (UroToday.com) Gordon Hong noted radical nephrectomy with removal of tumor thrombus is considered standard of care in patients with non-metastatic renal cell carcinoma (RCC). Surgical resection usually consists of nephrectomy and thrombectomy; however, ligation of the IVC is sometimes necessary. This study assessed the outcomes, particularly functional outcomes, in RCC patients undergoing IVC ligation compared to caval thrombectomy.

They conducted a case-controlled, retrospective study at a high-volume single-center institution. All RCC patients undergoing ligation were matched with thrombectomy patients in a 1:2 ratio based on pre-operative renal function, Charlson Comorbidity Index (CCI), and race. Endpoints were complications, changes in renal function, and mortality.

A total of 20 IVC ligation patients were matched with 40 thrombectomy patients. Median follow-up time was 15.3 months for both groups. There was no statistical difference in major complications (Clavien-Dindo Grade 3a+) between cohorts in their postoperative hospital stay (p=0.345) or at 3 months (p=0.464). Average decline in estimated glomerular filtration rate (eGFR) from baseline to 6-months post-surgery for ligation and thrombectomy was 4.6 mL/min/1.73m2 and 6.0 mL/min/1.73m2, respectively (p=0.767). The difference in the likelihood of lymphedema development (OR 0.15, 95% CI: 0.02-1.03, p=0.054) was not statistically significant, though more ligation patients experienced lymphedema development. Moreover, differences in all-cause mortality (p=0.197) and cancer-specific mortality (p=1.00) were also not statistically significant at all time points.

This study represents one of the largest cohort of RCC patients undergoing IVC ligation to date. Although IVC ligation patients experience more complications, they have similar functional and oncologic outcomes. These data are useful for patient counseling and representative of a single high volume surgeon experience which findings may not be generalizable to others

Presented by:Gordon Hong, BS, Emory University School of Medicine, Atlanta, Georgia

Written by: Stephen B. Williams, MD, Medical Director for High Value Care; Chief of Urology, Associate Professor, Director of Urologic Oncology, Director Urologic Research, The University of Texas Medical Branch at Galveston, TX atthe2019 American College of Surgeons (ACS), #ACSCC19, October 2731 in San Francisco, California

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ACS 2019: Outcomes in Renal Cell Carcinoma (RCC) Patients Undergoing Inferior Vena Cava (IVC) Ligation versus Thrombectomy: A Retrospective,...