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Are TAVR volume requirements limiting rural and minority access to this life-saving procedure, or are they still necessary for patient safety?

Reporter: Aviva Lev-Ari, PhD, RN

 

CMS Considers Changing TAVR Volume Requirements

Debate over transcatheter aortic valve replacement (TAVR) procedures continues as the Centers for Medicare and Medicaid Services (CMS) considers changing the status quo. Are TAVR volume requirements limiting rural and minority access to this life-saving procedure, or are they still necessary for patient safety?

In June 2018, cardiology news sources widely reported that CMS opened public comment on established volume requirements for hospitals and heart teams to perform TAVR. The Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) then met on July 25 to discuss the issue. A report in Cardiovascular Business suggested that the committee appeared split on the subject—especially in weighing the potential harms of limiting TAVR to only high volume hospitals.

Cases for and against TAVR volume requirements

The Case for TAVR Volume Requirements

For those on the side of maintaining TAVR volume requirements, the benefits are obvious—volume is associated with positive outcomes and lower rates of complications. In fact, a 2018 expert consensus document from four major cardiology societies actually supported increasing volume requirements to maintain a TAVR program, to ensure adequate data collection for statistically reliable quality metrics and quality assurance.

A new study published in September in JACC: Cardiovascular Interventions seems to add new weight to this argument—data collected from hospitals participating in the international TAVR registry showed volume to have a significant effect on patient safety. The findings suggested that a learning curve of at least 225 procedures was required for hospitals to perform TAVRs with the lowest mortality rates, and that low annual volume hospitals were associated with decreased procedural safety and higher patient mortality.

John D. Carroll, MD, of the University of Colorado School of Medicine wrote an editorial in the same publication arguing that there is a “danger of lowering TAVR quality of care” by relaxing or eliminating TAVR volume requirements. “This would create many new centers starting a new learning curve, result in more low-volume centers, and potentially diluting the case volume and advanced skills of established and high-volume centers,” he writes.

The Case Against TAVR Volume Requirements

While the case for TAVR volume requirements is strong, it does little to answer the central question of the opposing viewpoint—does the benefit of expanding TAVR access to rural areas outweigh the cost of allowing the procedure to be conducted in relatively inexperienced or low-volume centers?

It is difficult to capture data depicting how many patients with aortic stenosis go without valve replacement due to TAVR volume requirements, but the concern seems genuine. We continue to learn more about TAVR, but experts have already established the procedure as the “treatment of choice in the extreme-risk patient who cannot have surgery,” said Martin B. Leon, MD, FACC at a 2017 American College of Cardiology conference.

In this population, where surgical valve replacement is not an option, median life expectancy is increased from 11 months to almost 30 months with TAVR, according to Leon. Indeed, some experts like Deepak L. Bhatt, MD, MPH, FACC, believe that, regardless of surgical risk scores, patients over 80 should undergo TAVR rather than surgical valve replacements.

If TAVR volume requirements limit access to the procedure for this growing elderly population, the negative effects would be obvious. An Edwards Lifesciences resource about aortic stenosis states, “After the onset of symptoms, patients with severe aortic stenosis have a survival rate as low as 50% at 2 years.”

SOURCE

https://acp-online.org/tavr-volume-requirements-debate/

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Will the Supreme Court accept a UC Berkeley Appeal of the Sep. 10th, US Court of Appeals for the Federal Circuit decision to uphold the patent filed by the Broad Institute on CRISPR/Cas9 gene editing?

Reporter: Aviva Lev-Ari, PhD, RN

 

On 2018, Sep. 10th, the US Court of Appeals for the Federal Circuit agreed to uphold the patent filed by the Broad Institute on CRISPR/Cas9 gene editing in organisms with complex cells – UC Berkeley team can appeal this decision to the US Supreme Court, it is unclear whether the Supreme Court will accept this case.

According to Appeal and Interference Statistics 11/30/2016

https://www.uspto.gov/sites/default/files/documents/Appeal%20and%20Interference%20Statistics%20November%202016.pdf

In recent years, more than half of PTAB’s decisions have been upheld. “The Federal Circuit heard three appeals of interferences in 2016,” said intellectual property expert Jacob Sherkow of New York Law School. “All three were at least affirmed in part. It’s completely unclear whether that’s meaningful — it’s an N of 3–but there you go.” Overall, on 155 appeals since PTAB was created in 2012, the Federal Circuit affirmed 120 on every issue, dismissed or reversed 21 on every issue, and issued partial decisions (that is, upholding parts of a PTAB decision and reversing others) in the other 14.

SOURCE

Disputed CRISPR Patents Stay with Broad Institute, U.S. Panel Rules

Three judges have released their decision

https://www.scientificamerican.com/article/disputed-crispr-patents-stay-with-broad-institute-u-s-panel-rules/

 

Based on

Appeal and Interference Statistics 11/30/2016

https://www.uspto.gov/sites/default/files/documents/Appeal%20and%20Interference%20Statistics%20November%202016.pdf

I recommend UC, Berkeley to Appeal to the Supreme Court the Sept 10th Decision.


Cancer Cell Therapy: Global Start up Acquisitions in Oncolytic Viruses (OV) Therapeutics – a Pipeline of 70 OVs in Clinical Development and another 95 in Preclinical Programs

 

Reporter: Aviva Lev-Ari, PhD, RN

 

September 2018 

  • Boehringer Ingelheim is buying ViraTherapeutics in $244M deal

Boehringer Ingelheim joins the crowd and goes all-in on oncolytic viruses, buying ViraTherapeutics in $244M deal

https://endpts.com/boehringer-ingelheim-joins-the-crowd-and-goes-all-in-on-oncolytic-viruses-buying-viratherapeutics-in-244m-deal/?utm_medium=email&utm_campaign=Thursday%20September%2013%202018&utm_content=Thursday%20September%2013%202018+CID_61414a80a0003abe24ea7e26fafb3eab&utm_source=ENDPOINTS%20emails&utm_term=Boehringer%20Ingelheim%20joins%20the%20major%20league%20players%20with%20a%20buyout

 

May 2018

  • J&J executed one of its classic billion-dollar deals to buy BeneVir.

J&J’s Janssen to Acquire BeneVir for $1 Billion

May 09, 2018
By Pharmaceutical Technology Editors

Janssen Biotech, part of Janssen Pharmaceutical Companies, a subsidiary of Johnson & Johnson (J&J), announced on May 2, 2018 that it has entered into a definitive agreement to acquire BeneVir Biopharm (BeneVir), a biotechnology company specializing in the development of oncolytic immunotherapies.

BeneVir is a portfolio company and subsidiary of HC2 Holdings’ Pansend Life Sciences, which is focused on developing healthcare technologies and products. Benevir uses a proprietary T-Stealth Oncolytic Virus Platform to engineer oncolytic viruses tailored to infect and eliminate cancer cells.

Under the terms of the agreement, Janssen will make an upfront cash payment of $140 million at closing of the transaction, plus additional contingent payments of up to $900 million based on achievement of certain predetermined milestones. The total amount of all payments could exceed $1 billion if all milestones are met. The closing of the transaction is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act. The transaction, which was facilitated by J&J Innovation, is expected to close in the second quarter of 2018.

SOURCE

http://www.pharmtech.com/jj-s-janssen-acquire-benevir-1-billion-0

 

May 2018

  • A recent study from the Cancer Research Institute found 69 OVs in clinical development and another 95 in a preclinical program.

New Report on the Global Landscape of Cancer Cell Therapy Highlights Robust International Pipeline Marked by Rapid Growth

  • A comprehensive, neutral analysis of the global cancer cell therapy landscape
  • 753 cancer cell therapies in the global development pipeline, with 375 in clinical studies
  • 350 new cancer cell therapies have entered the global development pipeline since Sep. 2017, an 87% increase in less than 7 months
  • 113 targets are being pursued in 7 different classes of cell therapies

NEW YORK, May 25, 2018—The Cancer Research Institute (CRI) announced today the publication of a report that provides a comprehensive, independent analysis of the global landscape of cancer cell therapies, including all agents from preclinical to post-market stages. This report provides a quantitative and current overview of the cancer cell therapy field, reveals the unparalleled speed of the field’s expansion, highlights exciting innovations in the development pipeline, and advises strategies to advance the field as a whole.

The report, titled “The Global Landscape of Cancer Cell Therapy,” appeared online today in Nature Reviews Drug Discovery, a premium journal from Nature Publishing Group and an authoritative source of information in drug discovery and development. This report, which expands on CRI’s previously published landscape analysis of the entire field of immuno-oncology, highlights the geographic distribution of cancer cell therapies worldwide and identifies the dominant presence of CAR T therapies in the cancer cell therapy space.

“The quantitative analyses from this report reveal unprecedented enthusiasm and innovation in the global cell therapy pipeline,” said Jill O’Donnell-Tormey, Ph.D., chief executive officer and director of scientific affairs at the Cancer Research Institute.

“In addition to traditional powerhouses of drug development such as the United States or European countries, many other countries, especially China, have significant presence in this space,” noted Jun Tang, Ph.D., a senior research analyst for the CRI Anna-Maria Kellen Clinical Accelerator program and first author on the report.

To access the interactive dashboard of the report, visit the CRI website at cancerresearch.org/io-cell-therapy.

Reference
Tang J. et al. Global landscape of cancer cell therapy. Nature Reviews Drug Discovery. 25 May 2018. doi:10.1038/nrd.2018.74

SOURCE

https://www.cancerresearch.org/news/2018/global-landscape-of-cancer-cell-therapy-report

 

February 2018

  • Merck’s R&D chief Roger Perlmutter — who steered the T-Vec deal at Amgen — bagged Viralytics for $394 million.
FEBRUARY 21, 2018 / 4:29 AM / 7 MONTHS AGO

Merck to buy virus-based cancer drug firm Viralytics for $394 million

(Reuters) – U.S. drugmaker Merck & Co (MRK.N), already one of the leaders in the hot area of cancer immunotherapy, said on Wednesday it had agreed to buy Viralytics VLA.AX for 502 million Australian dollars ($394 million) to expand its pipeline in the sector.

Merck will pay 1.75 Australian dollars per share for the Sydney-based biotech company, which uses viruses to infect and kill cancer cells.

The idea is to cause cancer cells to rupture and die, while also stimulating a wider immune system response in the body.

SOURCE

https://www.reuters.com/article/us-viralytics-m-a-merck-co/merck-to-buy-virus-based-cancer-drug-firm-viralytics-for-394-million-idUSKCN1G50ZN

 

Hum Vaccin Immunother. 2018; 14(4): 839–846.
Published online 2018 Feb 22. doi:  10.1080/21645515.2017.1412896
PMCID: PMC5893211
PMID: 29420123

Talimogene laherparepvec: First in class oncolytic virotherapy

ABSTRACT

Oncolytic viruses represent a novel drug class in which native or modified viruses mediate tumor regression through selective replication within and lysis of tumor cells as well as induction of systemic antitumor immunity capable of eradicating tumor at distant, uninjected sites. Talimogene laherparepvec (TVEC) is a type I herpes simplex virus genetically modified to preferentially replicate in tumor cells, enhance antigen loading of MHC class I molecules and express granulocyte-macrophage colony-stimulating factor to increase tumor-antigen presentation by dendritic cells. It is presently the only oncolytic virus approved by the FDA with an indication for advanced melanoma based upon improved durable response rate in a randomized, phase III trial. Clinical trials are underway in melanoma investigating TVEC as neoadjuvant monotherapy and in combination with checkpoint inhibitors for unresectable disease as well as in an array of other malignancies. It is appropriate to review TVEC’s biology mechanism of action, clinical indication and future directions as a prototype of the burgeoning class of oncolytic viruses.

SOURCE

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893211/

October 2015 

  • Amgen’s landmark approval of T-Vec, the world’s first marketed oncolytic virus.

FDA approves cancer-killing cold sore virus as therapy for late-stage melanoma

October 28, 2015, University of Utah Health Sciences
melanoma
Melanoma in skin biopsy with H&E stain — this case may represent superficial spreading melanoma. Credit: Wikipedia/CC BY-SA 3.0

The U.S. Food and Drug Administration announced on Oct. 27 that it has approved, for the first time, an oncolytic (cancer-killing) viral therapy in the United States. The drug was approved for use against late-stage melanoma, a deadly skin cancer that can be difficult to treat.

The approval came as the result of a recent Phase III study, which showed that more patients with late-stage melanoma, treated with a herpes cold sore virus designed to kill , had a better response when compared to a different treatment. Robert Andtbacka, M.D., from Huntsman Cancer Institute at the University of Utah and Howard L. Kaufman, M.D., from Rutgers Cancer Institute of New Jersey, led the multisite study, published May 26 online in the Journal of Clinical Oncology.

SOURCE

https://medicalxpress.com/news/2015-10-fda-cancer-killing-cold-sore-virus.html

 

Additional Sources

T Cell Engineering Breakthrough Sidesteps Need for Viruses in Gene-Editing
UCSF News Center | Pete Farley | July 11, 2018

With Faster, Cheaper, More Precise Technique, Authors Say It’s ‘Off to the Races’ Toward New Cell

The basic unit of life. The number of cells in a living organism ranges from one (e.g. yeast) to quadrillions (e.g. blue whale). A cell is composed of four key macromolecules that allow it to function (protein, lipids, carbohydrates, and nucleic acids). Among other things, cells can build and break down molecules, move, grow, divide, and die.

” aria-describedby=”tt”>CellTherapies

In an achievement that has significant implications for research, medicine, and industry, UC San Francisco scientists have genetically reprogrammed the human immune cells known as T cells without using Virus

An infectious entity that can only persist by hijacking a host organism to replicate itself. Has its own genome, but is technically not considered a living organism. Viruses infect all organisms, from humans to plants to microbes. Multicellular organisms have sophisticated immune systems that combat viruses, while CRISPR systems evolved to stop viral infection in bacteria and archaea.

” aria-describedby=”tt”>viruses to insert DNA

Abbreviation of deoxyribonucleic acid, a long molecule that encodes the information needed for a cell to function or a virus to replicate. Forms a double-helix shape that resembles a twisted ladder. Different chemicals called bases, abbreviated as A, C, T, and G, are found on each side of the ladder, or strand. The bases have an attraction for each other, making A stick to T while C sticks to G. These rungs of the ladder are called base pairs. The sequence of these letters is called the genetic code.

” aria-describedby=”tt”>DNA. The researchers said they expect their technique — a rapid, versatile, and economical approach employing CRISPR

Pronounced “crisper.” An adaptive immune system found in bacteria and archaea, co-opted as a genome engineering tool. Acronym of “clustered regularly interspaced short palindromic repeats,” which refers to a section of the host genome containing alternating repetitive sequences and unique snippets of foreign DNA. CRISPR-associated surveillance proteins use these unique sequences as molecular mugshots as they seek out and destroy viral DNA to protect the cell.

” aria-describedby=”tt”>CRISPR Gene

A segment of DNA that encodes the information used to make a protein. Each gene is a set of instructions for making a particular molecular machine that helps a cell, organism, or virus function.

” aria-describedby=”tt”>gene-editing technology — to be widely adopted in the burgeoning field of cell therapy, accelerating the development of new and safer treatments for Cancer

A type of disease caused by uncontrolled growth of cells. Cancerous cells may form clumps or masses known as tumors, and can spread to other parts of the body through a process known as metastasis.

” aria-describedby=”tt”>cancer, autoimmunity, and other diseases, including rare inherited disorders.

The new method, described in the July 11, 2018 issue of Nature, offers a robust molecular “cut and paste” system to rewrite Genome

The entire DNA sequence of an organism or virus. The genome is essentially a huge set of instructions for making individual parts of a cell and directing how everything should run.

” aria-describedby=”tt”>genome sequences in human T cells. It relies on electroporation, a process in which an electrical field is applied to cells to make their membranes temporarily more permeable. After experimenting with thousands of variables over the course of a year, the UCSF researchers found that when certain quantities of T cells, DNA, and the CRISPR “scissors” are mixed together and then exposed to an appropriate electrical field, the T cells will take in these elements and integrate specified genetic sequences precisely at the site of a CRISPR-programmed cut in the genome.

“This is a rapid, flexible method that can be used to alter, enhance, and reprogram T cells so we can give them the specificity we want to destroy cancer, recognize infections, or tamp down the excessive immune response seen in autoimmune disease,” said UCSF’s Alex Marson, MD, PhD, associate professor of microbiology and immunology, member of the UCSF Helen Diller Family Comprehensive Cancer Center, and senior author of the new study. “Now we’re off to the races on all these fronts.”

But just as important as the new technique’s speed and ease of use, said Marson, also scientific director of biomedicine at the Innovative Genomics

The study of the genome, all the DNA from a given organism. Involves a genome’s DNA sequence, organization and control of genes, molecules that interact with DNA, and how these different components affect the growth and function of cells.

” aria-describedby=”tt”>Genomics Institute, is that the approach makes it possible to insert substantial stretches of DNA into T cells, which can endow the cells with powerful new properties. Members of Marson’s lab have had some success using electroporation and CRISPR to insert bits of genetic material into T cells, but until now, numerous attempts by many researchers to place long sequences of DNA into T cells had caused the cells to die, leading most to believe that large DNA sequences are excessively toxic to T cells.

SOURCE

https://innovativegenomics.org/news/t-cell-engineering-breakthrough-sidesteps-viruses/

 

Cancer Res. 2016 Aug 15; 76(16): 4627–4636.

Published online 2016 Jun 3. doi:  10.1158/0008-5472.CAN-15-3455

PMCID: PMC5295843

CAMSID: CAMS5780

PMID: 27261504

Design and Reporting of Targeted Anticancer Preclinical Studies: A Meta-Analysis of Animal Studies Investigating Sorafenib Antitumor Efficacy

James Mattina,1 Nathalie MacKinnon,1 Valerie C. Henderson,1 Dean Fergusson,2 andJonathan Kimmelman

 

Other 17 related articles published in this Online Scientific Journal include the following:

https://pharmaceuticalintelligence.com/category/oncolytic-virus-oncoviro-therapy/

Posted in BioTechnology - Venture Creation, BioTechnology - Venture Creation, Venture Capital, Oncolytic virus & OncoViro-Therapy | Leave a Comment »

Entrepreneurship in Biotech – Read this book!!!


Entrepreneurship in Biotech – Read this book!!!

Reporter: Aviva Lev-Ari, PhD, RN

 

ARE YOU INTERESTED IN #Entrepreneurship in Biotech??? – Read this book!!!

Hammer and Silicon: The Soviet Diaspora in the US Innovation Economy – Immigration, Innovation, Institutions, Imprinting, and Identity

by Sheila M. Puffer (Author), Daniel J. McCarthy  (Author), Daniel M. Satinsky  (Author)

Paperback – June 30, 2018

https://www.amazon.com/Hammer-Silicon-Innovation-Immigration-Institutions/dp/1316641260/ref=sr_1_1?s=books&ie=UTF8&qid=1536715051&sr=1-1&keywords=Hammer+and+SIlicon

Posted in BioTechnology - Venture Creation, Venture Capital | Leave a Comment »

Extraordinary Breakthrough in Artificial Eyes and Artificial Muscle Technology


Extraordinary Breakthrough in Artificial Eyes and Artificial Muscle Technology

Reporter: Irina Robu, PhD

Metalens, flat surface that use nanostructures to focus light promise to transform optics by replacing the bulky, curved lenses presently used in optical devices with a simple, flat surface.

Scientists at the Harvard John A. Paulson School of Engineering and Applied Sciences designed metalens who are mainly focused on light and minimizes spherical aberrations through a dense pattern of nanostructures, since the information density in each lens will be high due to nanostructures being small.

According to Federico Capasso, “This demonstrates the feasibility of embedded optical zoom and auto focus for a wide range of applications, including cell phone cameras, eyeglasses, and virtual and augmented reality hardware. It also shows the possibility of future optical microscopes, which operate fully electronically and can correct many aberrations simultaneously.”

However, when scientists tried to scale up the lens, the file size of the design alone would balloon up to gigabytes or even terabytes. And as a result, create a new algorithm in order to shrivel the file size to make the metalens flawless with the innovation currently used to create integrated circuits. Afterward, scientists follow the large metalens to an artificial muscle without conceding its ability to focus light. In the human eye, the lens is enclosed by ciliary muscle, which stretches or compresses the lens, changing its shape to adjust its focal length. Scientists at that moment choose a thin, transparent dielectric elastomer with low to attach to the lens.

Within the experiment, when the voltage is applied to elastomers, it stretches, the position of nanopillars on the surface of the lens shift. The scientists as a result show that the lens can focus instantaneous, control abnormalities triggered by astigmatisms, and achieve image shift. Since the adaptive metalens is flat, you can correct those deviations and assimilate diverse optical capabilities onto a single plane of control.

SOURCE

https://news.harvard.edu/gazette/story/2018/02/researchers-combine-artificial-eye-and-artificial-muscle

Posted in Medical Devices R&D and Inventions, Nanotechnology for Drug Delivery, Physics, Uncategorized | Tagged , , , , | Leave a Comment »

Sickle Cell and Beta Thalassemia chosen for first human trial of the gene editing technology, CRISPR by sponsoring companies CRISPR Therapeutics and Vertex Pharmaceuticals, trial at a single site in Germany, 


Sickle Cell and Beta Thalassemia chosen for first human trial of the gene editing technology, CRISPR by sponsoring companies CRISPR Therapeutics and Vertex Pharmaceuticals, trial at a single site in Germany,

 

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 9/13/2018

 

September 13, 2018

NIH launches initiative to accelerate genetic therapies to cure sickle cell disease

“Our scientific investments have brought us to a point where we have many tools available to correct or compensate for the defective gene that causes sickle cell disease. We are now ready to use these tools to speed up our quest for a cure,” said Gary H. Gibbons, M.D., director of NIH’s National Heart, Lung, and Blood Institute (NHLBI), which is leading the effort.

SOURCE

https://www.nih.gov/news-events/news-releases/nih-launches-initiative-accelerate-genetic-therapies-cure-sickle-cell-disease

 

 

Vertex licensed CTX001, an autologous gene-edited hematopoietic stem cell therapy, from CRISPR in December. It was the first CRISPR-based treatment to come out of a four-year, $105 million deal the pair struck in 2015. At the time, Vertex paid up $75 million in cash and took a $30 million stake in CRISPR Therapeutics in exchange for the right to license up to six gene-editing programs. CTX001 is being developed for the blood disorders sickle cell disease and beta thalassemia.

Both disorders are caused by mutations in the beta-globin gene, which codes for a part of hemoglobin, the oxygen-carrying component of red blood cells. This results in missing or defective hemoglobin. CTX001 was developed on the knowledge that fetal hemoglobin—found in newborn babies but later replaced by adult hemoglobin—can be protective in adults who have blood disorders.

CTX001 uses CRISPR gene-editing ex vivo—that is, outside the body. A patient’s cells are harvested and edited to increase fetal hemoglobin levels in the patient’s blood cells. The edited cells are then infused back into the patient where they are expected to produce blood cells with fetal hemoglobin and compensate for defective adult hemoglobin.

SOURCE

https://www.fiercebiotech.com/biotech/crispr-therapeutics-vertex-start-first-company-backed-human-crispr-trial?mkt_tok=eyJpIjoiTm1FMllXTmtOMlkwWkRNdyIsInQiOiJLMUEyeGtsT0ZMTVBuM1RtbVFjRFdMQUdRcDZkXC9yVHlXTWxIQmlvc3M0XC9LVFArdlFuaVVYY0lQXC81ak9cL3h1VjFHYnprZ3dqVlNlaWFldWxcLzA3QUphdExpc0w0Vk1TSGR3WVl0YXNqQlFRVHdvZmNycVNEWE9qdWQ2QmdacklSIn0%3D&mrkid=993697

Other 339 articles on GENE EDITING were published in this Open Access Online Scientific Journal, including the following articles:

https://pharmaceuticalintelligence.com/?s=Gene+Editing

On CRISPR/Cas9, there are 141 articles in the Journal:

https://pharmaceuticalintelligence.com/?s=CRISPR%2FCas9

Gene Therapy, there are 11 articles in the Journal:

https://pharmaceuticalintelligence.com/category/genome-biology/gene-therapy-gene-editing-development/

Posted in CRISPR/Cas9 & Gene Editing, Gene Therapy & Gene Editing Development, Genome Biology | Leave a Comment »

Single-cell Genomics: Directions in Computational and Systems Biology – Contributions of Prof. Aviv Regev @Broad Institute of MIT and Harvard, Cochair, the Human Cell Atlas Organizing Committee with Sarah Teichmann of the Wellcome Trust Sanger Institute


Single-cell Genomics: Directions in Computational and Systems Biology – Contributions of Prof. Aviv Regev @Broad Institute of MIT and Harvard, Cochair, the Human Cell Atlas Organizing Committee with Sarah Teichmann of the Wellcome Trust Sanger Institute

 

Curator: Aviva Lev-Ari, PhD, RN

 

Dana Pe’er, PhD, now chair of computational and systems biology at the Sloan Kettering Institute at the Memorial Sloan Kettering Cancer Center and a member of the Human Cell Atlas Organizing Committee,

what really sets Regev apart is the elegance of her work. Regev, says Pe’er, “has a rare, innate ability of seeing complex biology and simplifying it and formalizing it into beautiful, abstract, describable principles.”

Dr. Aviv Regev, an MIT biology professor who is also chair of the faculty of the Broad and director of its Klarman Cell Observatory and Cell Circuits Program, was reviewing a newly published white paper detailing how the Human Cell Atlas is expected to change the way we diagnose, monitor, and treat disease at a gathering of international scientists at Israel’s Weizmann Institute of Science, 10/2017.

For Regev, the importance of the Human Cell Atlas goes beyond its promise to revolutionize biology and medicine. As she once put it, without an atlas of our cells, “we don’t really know what we’re made of.”

Regev, turned to a technique known as RNA interference (she now uses CRISPR), which allowed her to systematically shut genes down. Then she looked at which genes were expressed to determine how the cells’ response changed in each case. Her team singled out 100 different genes that were involved in regulating the response to the pathogens—some of which weren’t previously known to be involved in immune function. The study, published in Science, generated headlines.

The project, the Human Cell Atlas, aims to create a reference map that categorizes all the approximately 37 trillion cells that make up a human. The Human Cell Atlas is often compared to the Human Genome Project, the monumental scientific collaboration that gave us a complete readout of human DNA, or what might be considered the unabridged cookbook for human life. In a sense, the atlas is a continuation of that project’s work. But while the same DNA cookbook is found in every cell, each cell type reads only some of the recipes—that is, it expresses only certain genes, following their DNA instructions to produce the proteins that carry out a cell’s activities. The promise of the Human Cell Atlas is to reveal which specific genes are expressed in every cell type, and where the cells expressing those genes can be found.

Regev says,

The final product, will amount to nothing less than a “periodic table of our cells,” a tool that is designed not to answer one specific question but to make countless new discoveries possible.

Sequencing the RNA of the cells she’s studying can tell her only so much. To understand how the circuits change under different circumstances, Regev subjects cells to different stimuli, such as hormones or pathogens, to see how the resulting protein signals change.

“the modeling step”—creating algorithms that try to decipher the most likely sequence of molecular events following a stimulus. And just as someone might study a computer by cutting out circuits and seeing how that changes the machine’s operation, Regev tests her model by seeing if it can predict what will happen when she silences specific genes and then exposes the cells to the same stimulus.

By sequencing the RNA of individual cancer cells in recent years—“Every cell is an experiment now,” she says—she has found remarkable differences between the cells of a single tumor, even when they have the same mutations. (Last year that work led to Memorial Sloan Kettering’s Paul Marks Prize for Cancer Research.) She found that while some cancers are thought to develop resistance to therapy, a subset of melanoma cells were resistant from the start. And she discovered that two types of brain cancer, oligodendroglioma and astrocytoma, harbor the same cancer stem cells, which could have important implications for how they’re treated.

As a 2017 overview of the Human Cell Atlas by the project’s organizing committee noted, an atlas “is a map that aims to show the relationships among its elements.” Just as corresponding coastlines seen in an atlas of Earth offer visual evidence of continental drift, compiling all the data about our cells in one place could reveal relationships among cells, tissues, and organs, including some that are entirely unexpected. And just as the periodic table made it possible to predict the existence of elements yet to be observed, the Human Cell Atlas, Regev says, could help us predict the existence of cells that haven’t been found.

This year alone it will fund 85 Human Cell Atlas grants. Early results are already pouring in.

  • In March, Swedish researchers working on cells related to human development announced they had sequenced 250,000 individual cells.
  • In May, a team at the Broad made a data set of more than 500,000 immune cells available on a preview site.

The goal, Regev says, is for researchers everywhere to be able to use the open-source platform of the Human Cell Atlas to perform joint analyses.

Eric Lander, PhDthe founding director and president of the Broad Institute and a member of the Human Cell Atlas Organizing Committee, likens it to genomics.

“People thought at the beginning they might use genomics for this application or that application,” he says. “Nothing has failed to be transformed by genomics, and nothing will fail to be transformed by having a cell atlas.”

“How did we ever imagine we were going to solve a problem without single-cell resolution?”

SOURCE

https://www.technologyreview.com/s/611786/the-cartographer-of-cells/?utm_source=MIT+Technology+Review&utm_campaign=Alumni-Newsletter_Sep-Oct-2018&utm_medium=email

Other related articles published in this Open Access Online Scientific Journal include the following:

 

University of California Santa Cruz’s Genomics Institute will create a Map of Human Genetic Variations

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/01/13/university-of-california-santa-cruzs-genomics-institute-will-create-a-map-of-human-genetic-variations/

 

Recognitions for Contributions in Genomics by Dan David Prize Awards

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/31/recognitions-for-contributions-in-genomics-by-dan-david-prize-awards/

 

ENCODE (Encyclopedia of DNA Elements) program: ‘Tragic’ Sequestration Impact on NHGRI Programs

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/18/encode-encyclopedia-of-dna-elements-program-tragic-sequestration-impact-on-nhgri-programs/

 

Single-cell Sequencing

Genomic Diagnostics: Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single Molecule DNA Sequencing

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/04/genomic-diagnostics-three-techniques-to-perform-single-cell-gene-expression-and-genome-sequencing-single-molecule-dna-sequencing/

 

LIVE – Real Time – 16th Annual Cancer Research Symposium, Koch Institute, Friday, June 16, 9AM – 5PM, Kresge Auditorium, MIT – See, Aviv Regev

REAL TIME PRESS COVERAGE & Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/03/13/16th-annual-cancer-research-symposium-koch-institute-friday-june-16-9am-5pm-kresge-auditorium-mit/

 

LIVE 11/3/2015 1:30PM @The 15th Annual EmTech MIT – MIT Media Lab: Top 10 Breakthrough Technologies & 2015 Innovators Under 35 – See, Gilead Evrony

REAL TIME PRESS COVERAGE & Reporter: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2015/11/03/live-1132015-130pm-the-15th-annual-emtech-mit-mit-media-lab-top-10-breakthrough-technologies-2015-innovators-under-35/

 

Cellular Guillotine Created for Studying Single-Cell Wound Repair

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2017/06/29/cellular-guillotine-created-for-studying-single-cell-wound-repair/

 

New subgroups of ILC immune cells discovered through single-cell RNA sequencing

Reporter: Stephen J Williams, PhD

https://pharmaceuticalintelligence.com/2016/02/17/new-subgroups-of-ilc-immune-cells-discovered-through-single-cell-rna-sequencing-from-karolinska-institute/

 

#JPM16: Illumina’s CEO on new genotyping array called Infinium XT and Bio-Rad Partnership for single-cell sequencing workflow

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/12/jpm16-illuminas-ceo-on-new-genotyping-array-called-infinium-xt-and-bio-rad-partnership-for-single-cell-sequencing-workflow/

 

Juno Acquires AbVitro for $125M: high-throughput and single-cell sequencing capabilities for Immune-Oncology Drug Discovery

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/12/juno-acquires-abvitro-for-125m-high-throughput-and-single-cell-sequencing-capabilities-for-immune-oncology-drug-discovery/

 

NIH to Award Up to $12M to Fund DNA, RNA Sequencing Research: single-cell genomics,  sample preparation,  transcriptomics and epigenomics, and  genome-wide functional analysis.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/10/27/nih-to-award-up-to-12m-to-fund-dna-rna-sequencing-research-single-cell-genomics-sample-preparation-transcriptomics-and-epigenomics-and-genome-wide-functional-analysis/

 

Genome-wide Single-Cell Analysis of Recombination Activity and De Novo Mutation Rates in Human Sperm

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

https://pharmaceuticalintelligence.com/2012/08/07/genome-wide-single-cell-analysis-of-recombination-activity-and-de-novo-mutation-rates-in-human-sperm/

REFERENCES to Original studies

In Science, 2018

Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors

 See all authors and affiliations

Science  21 Apr 2017:
Vol. 356, Issue 6335, eaah4573
DOI: 10.1126/science.aah4573
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis

See all authors and affiliations

Science  26 Apr 2018:
eaar3131
DOI: 10.1126/science.aar3131

In Nature, 2018 and 2017

How to build a human cell atlas

Aviv Regev is a maven of hard-core biological analyses. Now she is part of an effort to map every cell in the human body.

https://www.nature.com/news/how-to-build-a-human-cell-atlas-1.22239
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Posted in Cancer Informatics, Computational Biology/Systems and Bioinformatics, Gene Regulation, Gene Regulation and Evolution, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Testing: Methodology for Diagnosis, mRNA Therapeutics, Mutagenesis, Single Cell Genomics, Single-cell sequencing, Variation in human protein-coding regions | Leave a Comment »