Bloomberg covers important investor interest in gene editing therapyBloomberg covers important investor interest in gene editing therapy

Biotech Investors Zero In on Gene Therapy as Next Big Frontier

(Bloomberg) -- Biotech investors are bullish on the market for gene therapies, even though actual sales of a few existing drugs have so far failed to impress some Wall Street analysts. Fund managers and venture capitalists discussed their outlook for the technology in interviews in Boston, where investors gathered for the Cowen health-care conference. Investor interest in gene-therapy stocks is high, as investing has paid off this year. Roche Holding AG and Biogen Inc. recently snapped up a pair of drug developers, boosting speculation of more deals. Also, U.S. regulators say they expect to approve 10 to 20 new medicines by 2025, while insurers grapple with treatment costs that can run into the hundreds of thousands of dollars.

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Linking development and disease

Putting developmental diseases on the map

Most people use a map to understand the physical world around them. Now, genetic researchers have a map of their own to understand how developmental diseases work at the genetic level.  

In a recent study, UW graduate student Junyue Cao and Dr. Malte Spielmann from the Max Planck Institute profiled approximately 2 million cells from 61 mice embryos between 9 and 14 days old, resulting in a digital representation of how each cell type develops and its gene expression changes.

When a gene is between 9 and 14 days old, most cells that underlie major developmental diseases can be studied, according to Cao. With further application, Cao believes his study can be used as a reference to help other researchers understand how genetic diseases like autism, breast cancer, and parkinson’s disease develop in humans.

“If we can use this to comprehensively categorize the different cell states and their composition in disease or [the] aging process, then potentially, we can fully understand how they are generated in development and why there are different diseases and aging,” Cao said.

Cao and his team collected the largest single-cell dataset, Mouse Organogenesis Cell Atlas (MOCA), which consists of distinctions between individual cells. This dataset has recently been published and in this publication, the team created a genetic map of organ development.

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T-cell modification with CRISPR-Cpf1

Researchers engineer immune cells to fight cancer

Deep in the cells of the human immune system, DNA is constantly being replicated, transcribed and even mutated — but rarely does it change dramatically. Like every other living organism, humans and their genes developed from millions of years of evolutionary pruning.

But to Yale microbiologists, altering the entire genomes of T-cells — the body’s main offensive weapon against diseases such as cancer — is as simple as putting together a Lego set.

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Cancer cells switch to fast food

Researchers find epigenetic loss that changes how cells obtain energy from cancer

It has been known for decades that cancer cells have an altered metabolism, and it is seen in several biochemical pathways and in particular, in the way they get energy for their survival.

If healthy cells use the mitochondrial respiratory chain, tumors use aerobic glycolysis, a process that allows them to take energy quickly but depending on glucose. This phenomenon - known as the Warburg effect - is caused by several changes that take place during cell transformation.

Now, a new article describes an epigenetic injury found in human tumours which creates this altered path to take energy from the cancer. The study, published in Journal of Clinical Investigation Insight, is a new research carried out by the group led by Manel Esteller, professor of Genetics of the Faculty of Medicine and Health Sciences of the University of Barcelona (UB), ICREA researcher, coordinator of the Cancer Epigenetics and Biology Program at IDIBELL, and director of the Josep Carreras Institute.

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Population genomic and evolutionary modeling analyses find QTL relevant to global health (BMC Genomics)

Population genomic and evolutionary modeling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus

Stephen R. Doyle†Email authorView ORCID ID profile, Christopher J. R. Illingworth†, Roz Laing, David J. Bartley, Elizabeth Redman, Axel Martinelli, Nancy Holroyd, Alison A. Morrison, Andrew Rezansoff, Alan Tracey, Eileen Devaney, Matthew Berriman, Neil Sargison, James A. Cotton,and John S. Gilleard

BMC Genomics (Research Article)

Infections with helminths cause an enormous disease burden in billions of animals and plants worldwide. Large scale use of anthelmintics has driven the evolution of resistance in a number of species that infect livestock and companion animals, and there are growing concerns regarding the reduced efficacy in some human-infective helminths. Understanding the mechanisms by which resistance evolves is the focus of increasing interest; robust genetic analysis of helminths is challenging, and although many candidate genes have been proposed, the genetic basis of resistance remains poorly resolved.

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Head to Head: CRISPR Therapeutics AG (CRSP)’s versus Pain Therapeutics Inc. (NASDAQ:PTIE)

CRISPR Therapeutics AG (CRSP)’s Financial Results Comparing With Pain Therapeutics Inc. (NASDAQ:PTIE)

CRISPR Therapeutics AG (NASDAQ:CRSP) and Pain Therapeutics Inc. (NASDAQ:PTIE) compete with each other in the Biotechnology sector. We will analyze and contrast their risk, analyst recommendations, profitability, institutional ownership, dividends, earnings and valuation.

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Head to Head: PerkinElmer Inc. (NYSE:PKI) and Cancer Genetics Inc. (NASDAQ:CGIX)

Reviewing PerkinElmer Inc. (PKI)’s and Cancer Genetics Inc. (NASDAQ:CGIX)’s results

We will be comparing the differences between PerkinElmer Inc. (NYSE:PKI) and Cancer Genetics Inc. (NASDAQ:CGIX) as far as analyst recommendations, institutional ownership, profitability, risk, dividends, earnings and valuation are concerned. The two businesses are rivals in the Medical Laboratories & Research industry.

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Why don't we make heritable gene editing available to everybody?

We should not fear 'editing' embryos to enhance human intelligence, says leading geneticist George Church

One of the world’s leading geneticists says it will only be a matter of time before the genes of  human embryos are ‘edited’ to enhance their health and intelligence – and it is something we should embrace rather than fear.

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Head to Head: Seattle Genetics Inc. (SGEN) and Benitec Biopharma Limited (NASDAQ:BNTC)

Comparison of Seattle Genetics Inc. (SGEN) and Benitec Biopharma Limited (NASDAQ:BNTC)

We will be comparing the differences between Seattle Genetics Inc. (NASDAQ:SGEN) and Benitec Biopharma Limited (NASDAQ:BNTC) as far as risk, analyst recommendations, profitability, dividends, institutional ownership, earnings and valuation are concerned. The two businesses are rivals in the Biotechnology industry.

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Goals for improving cancer treatment in children

Ushering in the next generation of precision trials for pediatric cancer

Steven G. DuBois, Laura B. Corson, Kimberly Stegmaier, and Katherine A. Janeway

Science (Review article)

Abstract—Cancer treatment decisions are increasingly based on the genomic profile of the patient’s tumor, a strategy called “precision oncology.” Over the past few years, a growing number of clinical trials and case reports have provided evidence that precision oncology is an effective approach for at least some children with cancer. Here, we review key factors influencing pediatric drug development in the era of precision oncology. We describe an emerging regulatory framework that is accelerating the pace of clinical trials in children as well as design challenges that are specific to trials that involve young cancer patients. Last, we discuss new drug development approaches for pediatric cancers whose growth relies on proteins that are difficult to target therapeutically, such as transcription factors.

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EGFR is required for regeneration

Study uncovers genes that control process of whole-body regeneration

When it comes to regeneration, some animals are capable of amazing feats. If you cut off a salamander’s leg, it will grow back. When threatened, some geckos drop their tails to distract their predator, only to regrow them later.

Other animals take the process even further. Planarian worms, jellyfish, and sea anemones can actually regenerate their bodies after being cut in half.

Led by Assistant Professor of Organismic and Evolutionary Biology Mansi Srivastava, a team of researchers is shedding new light on how animals pull off the feat, along the way uncovering a number of DNA switches that appear to control genes for whole-body regeneration. The study is described in a March 15 paper in Science.

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Next Next Gen Detection of Structural Variants

Accurate detection of complex structural variations using single-molecule sequencing

Fritz J. Sedlazeck, Philipp Rescheneder, Moritz Smolka, Han Fang, Maria Nattestad, Arndt von Haeseler, and Michael C. Schatz

Nature Methods (Research article)

Abstract—Structural variations are the greatest source of genetic variation, but they remain poorly understood because of technological limitations. Single-molecule long-read sequencing has the potential to dramatically advance the field, although high error rates are a challenge with existing methods. Addressing this need, we introduce open-source methods for long-read alignment (NGMLR; https://github.com/philres/ngmlr) and structural variant identification (Sniffles; https://github.com/fritzsedlazeck/Sniffles) that provide unprecedented sensitivity and precision for variant detection, even in repeat-rich regions and for complex nested events that can have substantial effects on human health. In several long-read datasets, including healthy and cancerous human genomes, we discovered thousands of novel variants and categorized systematic errors in short-read approaches. NGMLR and Sniffles can automatically filter false events and operate on low-coverage data, thereby reducing the high costs that have hindered the application of long reads in clinical and research settings.

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Ed Yong gets punny about evolution in the Atlantic

This Is a Truly Lousy Experiment About Evolution

By placing feather-eating lice on white, black, and gray pigeons, researchers showed how the parasites change color to better blend in.

“Believing that it is always best to study some special group, I have, after deliberation, taken up domestic pigeons,” wrote one Charles Darwin in On the Origin of Species. Four years earlier, Darwin had taken to raising pigeons in his own dovecote, hobnobbing with other pigeon fanciers, and carefully measuring the birds. In the diverse breeds, with their fantails, feather-duster feet, and frilly backs, Darwin saw validation for his ideas about evolution. If people could artificially select for such astonishing diversity in just a few generations, nature was surely capable of far more over longer timescales.

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Introduction to organioids

What you need to know about organoids

By Chloe Reichel

Paola Arlotta, chair of and professor in the stem cell and regenerative biology department at Harvard University, is growing brain tissue in her lab. In recent years, scientists have developed new techniques that add another level to the two-dimensional tissue culture of yore (e.g., growing cells in a single layer in a petri dish). These cells grow and divide in three dimensions, ultimately giving rise to samples of tissue that resemble the organ itself. They’re called organoids, but many news headlines have described them as if they are real, live organs.

Take these headlines for example: “Scientists grow human brains in a dish” and “Scientists brew up the creepiest batches of brain balls yet.” While science is in its infancy, the headlines don’t reflect that, taking liberties in describing what organoids are and overstating their form and function.

“You imagine a mini brain in a dish — that’s not what these things are,” Arlotta stresses. That bears repeating: They’re not mini brains; they’re not brains in a dish. They’re brain organoids, simplified replicas with some of the features of the organ they model.

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Important reminder that your genome is your property

Your invaluable genome

Genomic data is the currency of a new era of medicine that promises incredible advances. Here, bioinformatician Nana Mensah explains why…

In the race for greatest medical revolution of the 21st century, genomics is undoubtedly a frontrunner. Those outside of the field, however, might still find themselves wondering: 'what's all the fuss about?' There are many reasons why genomics is revolutionary, but data is at the root of it all. As genomics is used more and more in mainstream care, it becomes ever more important to understand the great power and value of this new kind of data, writes Nana Mensah.

From cell to computer

While the word ‘genome’ refers to the entire sequence of DNA of an individual organism, the term ‘genomic data’ refers to its digital representation – a large data file resulting from the sequencing process.

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Cabozantinib added to the kidney cancer treatment arsenal

Cabozantinib Approval Expands Initial Treatment Options for Advanced Kidney Cancer

For patients with the most common type of kidney cancer, there is now a new approved use of the targeted therapy cabozantinib (Cabometyx®). In December 2017, the Food and Drug Administration (FDA) approved use of the drug as an initial, or first-line, treatment for patients with advanced renal cell carcinoma (RCC).

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The true number of human miRNAs

An estimate of the total number of true human miRNAs

Julia Alles, Tobias Fehlmann, Ulrike Fischer, Christina Backes, Valentina Galata, Marie Minet, Martin Hart, Masood Abu-Halima, Friedrich A Grässer,  Hans-Peter Lenhof, Andreas Keller, and Eckart Meese

Nucleic Acids Research (Research Article)

Abstract—While the number of human miRNA candidates continuously increases, only a few of them are completely characterized and experimentally validated. Toward determining the total number of true miRNAs, we employed a combined in silico high- and experimental low-throughput validation strategy. We collected 28 866 human small RNA sequencing data sets containing 363.7 billion sequencing reads and excluded falsely annotated and low quality data. Our high-throughput analysis identified 65% of 24 127 mature miRNA candidates as likely false-positives. Using northern blotting, we experimentally validated miRBase entries and novel miRNA candidates. By exogenous overexpression of 108 precursors that encode 205 mature miRNAs, we confirmed 68.5% of the miRBase entries with the confirmation rate going up to 94.4% for the high-confidence entries and 18.3% of the novel miRNA candidates. Analyzing endogenous miRNAs, we verified the expression of 8 miRNAs in 12 different human cell lines. In total, we extrapolated 2300 true human mature miRNAs, 1115 of which are currently annotated in miRBase V22. The experimentally validated miRNAs will contribute to revising targetomes hypothesized by utilizing falsely annotated miRNAs.

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Connecting chromatin states (Epigenetics) to structural variation in human genomes

Chromatin organization modulates the origin of heritable structural variations in human genome 

Tanmoy Roychowdhury and Alexej Abyzov

Nucleic Acids Research (Article)

Abstract

“Structural variations (SVs) in the human genome originate from different mechanisms related to DNA repair, replication errors, and retrotransposition. Our analyses of 26 927 SVs from the 1000 Genomes Project revealed differential distributions and consequences of SVs of different origin, e.g. deletions from non-allelic homologous recombination (NAHR) are more prone to disrupt chromatin organization while processed pseudogenes can create accessible chromatin. Spontaneous double stranded breaks (DSBs) are the best predictor of enrichment of NAHR deletions in open chromatin. This evidence, along with strong physical interaction of NAHR breakpoints belonging to the same deletion suggests that majority of NAHR deletions are non-meiotic i.e. originate from errors during homology directed repair (HDR) of spontaneous DSBs. In turn, the origin of the spontaneous DSBs is associated with transcription factor binding in accessible chromatin revealing the vulnerability of functional, open chromatin. The chromatin itself is enriched with repeats, particularly fixed Alu elements that provide the homology required to maintain stability via HDR. Through co-localization of fixed Alus and NAHR deletions in open chromatin we hypothesize that old Alu expansion had a stabilizing role on the human genome.”

Pediatric cancer mutation review

The genomic landscape of pediatric cancers: Implications for diagnosis and treatment

E. Alejandro Sweet-Cordero1 and Jaclyn A. Biegel

Science (Review Artice)

Abstract-The past decade has witnessed a major increase in our understanding of the genetic underpinnings of childhood cancer. Genomic sequencing studies have highlighted key differences between pediatric and adult cancers. Whereas many adult cancers are characterized by a high number of somatic mutations, pediatric cancers typically have few somatic mutations but a higher prevalence of germline alterations in cancer predisposition genes. Also noteworthy is the remarkable heterogeneity in the types of genetic alterations that likely drive the growth of pediatric cancers, including copy number alterations, gene fusions, enhancer hijacking events, and chromoplexy. Because most studies have genetically profiled pediatric cancers only at diagnosis, the mechanisms underlying tumor progression, therapy resistance, and metastasis remain poorly understood. We discuss evidence that points to a need for more integrative approaches aimed at identifying driver events in pediatric cancers at both diagnosis and relapse. We also provide an overview of key aspects of germline predisposition for cancer in this age group.

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Cancers are tissue-specific, truly important perspective

Tissue-specificity in cancer: The rule, not the exception

Kevin M. Haigis, Karen Cichowski, and Stephen J. Elledge

Science (article)

“Abstract—We are in the midst of a renaissance in cancer genetics. Over the past several decades, candidate-based targeted sequencing efforts provided a steady stream of information on the genetic drivers for certain cancer types. However, with recent technological advances in DNA sequencing, this stream has become a torrent of unbiased genetic information revealing the frequencies and patterns of point mutations and copy number variations (CNVs) across the entire spectrum of cancers. One of the most important observations from this work is that genetic alterations in bona fide cancer drivers (those genes that, when mutated, promote tumorigenesis) show a remarkable spectrum of tissue specificity”

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