The first step towards a "Cancer Dependency Map"

That most cancers use the same set of molecular tools is a very powerful idea, but it has been hard to figure out what these tools are and how to target them. Follow the link below for a quick, and enthusiastic, summary of genome-scale CRISPR–Cas9 screens of 324 human cancer cell lines from 30 cancer types with the goal of developing a new, diverse and more effective portfolio of cancer drug targets.

'Dismantling cancer' reveals weak spots

The first step towards a "Cancer Dependency Map"

James Gallagher, BBC News

Scientists have taken cancer apart piece-by-piece to reveal its weaknesses, and come up with new ideas for treatment. A team at the Wellcome Sanger Institute disabled every genetic instruction, one at a time, inside 30 types of cancer. It has thrown up 600 new cancer vulnerabilities and each could be the target of a drug.Cancer Research UK praised the sheer scale of the study.

The study heralds the future of personalised cancer medicine. At the moment drugs like chemotherapy cause damage throughout the body. One of the researchers is Dr Fiona Behan, whose mother died after getting cancer for the second time.


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CRISPR gene drive vs CRISPR allelic drive

CRISP-based genome modifying technologies are offer a power and precision people only dreamed of not that long ago. CRISPR gene drives use guide RNAs (gDNAs) to insert gene-drive sequences, and the CRISPR allele drives do the same while also modifying undesired variants at a second position. Gene and allele drives are likely to be central to how humans modify the living environment in the future, in addition to being the starting point for endless unchecked-tech sci-fi nightmare scenarios . The following article provides a clear and helpful explanation of these technologies and some of their applications.

CRISPR-based 'allelic drive' allows genetic editing with selective precision and broad implications

Difference between gene drive and allelic drive explained

Scientists developed a new version of a gene drive that allows the spread of specific, favorable genetic variants, also known as 'alleles,' throughout a population. The new 'allelic drive' is equipped with a guide RNA that directs CRISPR to cut undesired variants of a gene and replace it with a preferred version. Using a word processing analogy, CRISPR-based gene drives allow scientists to edit sentences of genetic information, while the new allelic drive offers letter-by-letter editing.


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CRISPR DNA "shredder"

New DNA 'shredder' technique goes beyond CRISPR's scissors

CRISPR DNA "shredder"

An international team has unveiled a new CRISPR-based tool that acts more like a shredder than the usual scissor-like action of CRISPR-Cas9. The new approach, based on Type I CRISPR-Cas3, is able to wipe out long stretches of DNA in human cells with programmable targeting, and has been shown to work in human cells for the first time.


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A bioengineer, a biopunk, and a biotech reporter talk about Genetic Engineering

The Future of Genetic Engineering

A bioengineer, a biopunk, and a biotech reporter square off onstage about our neobiological future.

By Jane Metcalfe

In a new documentary that is still in production, filmmaker Cory Sheehy follows renowned bioengineer George Church and biotech reporter Antonio Regalado to China for the 2nd International Summit on Human Genome Editing. That’s where biophysicist He Jiankui made the stunning announcement that he had edited the DNA of two twin girls who were born in November 2018. Back in California, the filmmaker catches up with biohacker Josiah Zayner, whose attention-grabbing exploits—part protest, part performance art—include injecting himself with a CRISPR-Cas9 plasmid.

Watch the video here …

Gene-Edited Anolis Lizards

UGA scientists create world’s first gene-edited lizards

Crispant-lizard.jpg

A group of University of Georgia researchers led by geneticist Douglas Menke has become the first in the world to successfully produce a genetically modified reptile—specifically, four albino lizards—using the CRISPR-Cas9 gene-editing tool. The team’s results, which appeared online March 31, have been submitted for peer review.

“Reptiles are very understudied in terms of their reproductive biology and embryonic development,” said Menke, associate professor in the department of genetics. “There are no good methods to manipulate embryos like we can easily do with mammals, fish or amphibians. To our knowledge, no other lab in the world has produced a genetically altered reptile.”

Gene manipulation using CRISPR typically involves injecting gene-editing solutions into an animal’s newly fertilized egg or single-cell embryo, causing a mutation in the DNA that is reproduced in all subsequent cells. However female reptiles can store sperm in their oviducts for long periods, making it difficult to pinpoint the exact moment of fertilization. Also, the physiology of their fertilized eggs, which have pliable shells with no air space inside, presents challenges for manipulating embryos without damaging them.

Working with the species Anolis sagrei, commonly called the brown anole, Menke’s team overcame these challenges by microinjecting CRISPR proteins into multiple immature eggs, or oocytes, still located in the lizards’ ovaries. Targeting the tyrosinase gene, they successfully injected 146 oocytes from 21 lizards, then waited for the oocytes to be fertilized naturally. Within a few weeks, they realized their goal: four offspring displaying the telltale trait of albinism, which results when tyrosinase is inactivated.


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CRISPR cut slows aging

Recently Developed Gene Therapy Assists To Slow Down Aging Process

CRISPR cut slows aging

Aging is a key risk factor for numerous debilitating conditions. It includes cancer, heart disease, and Alzheimer’s disease. This situation triggers the anti-aging treatments all the more critical. Recently, the researchers at Salk Institute proclaimed that they have developed a novel gene therapy to assist decelerate this aging process.

The findings of this research can be accessed in the journal Nature Medicine. The study highlights a new CRISPR/Cas9 genome-editing therapy. It holds an ability to curb the accelerated aging observed in mice suffering from Hutchinson-Gilford progeria syndrome. This is an uncommon genetic disorder that is found to be afflicting humans as well. The latest treatment offers key insight into the molecular pathways engaged in accelerated aging. It also highlights how to minimize toxic proteins using gene therapy. Juan Carlos Izpisua Belmonte, Professor, Gene Expression Laboratory, Salk, is the senior author of this study. He proclaimed that aging is a complicated process in which cells begin losing their functionality.


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Or read the original article HERE …

CRISPR cuts 13,000 times in one cell

Genome engineers made more than 13,000 CRISPR edits in a single cell

Rewriting Life

A team at George Church’s Harvard lab wants to redesign species with large-scale DNA changes.

by Antonio Regalado (MIT Technology Review)

Since its invention, CRISPR has let scientists introduce DNA changes at specific locations in a genome. Often these precise changes are made one at a time.

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Perhaps not for much longer. A team at Harvard University says it has used the technique to make 13,200 genetic alterations to a single cell, a record for the gene-editing technology.

The group, led by gene technologist George Church, wants to rewrite genomes at a far larger scale than has currently been possible, something it says could ultimately lead to the “radical redesign” of species—even humans. Large-scale gene editing of this sort has been tried before. In 2017, an Australian team led by Paul Thomas peppered the Y chromosome of mice with edits and succeeded in blasting it out of existence. That strategy is being eyed as a potential treatment for Down syndrome, a genetic disorder caused by an extra chromosome.


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Promise of cheap and fast CRISPR-based diagnostics

Handheld CRISPR device to enable faster diagnosis of genetic disease

Promise of cheap and fast CRISPR-based diagnostics

A team of researchers in the US has developed a handheld device that diagnoses genetic diseases at point-of-care. Called CRISPR-Chip, the device combines a deactivated clustered regularly interspaced short palindromic repeats (CRISPR) Cas9 protein with electronic transistors to identify genetic mutations in DNA samples without the need for amplification or replication of the DNA segment using the polymerase chain reaction (PCR).

Avoiding the time-consuming PCR step is expected to enable the use of CRISPR-Chip for genetic testing in a doctor’s office or field work setting, rather than sending samples to a laboratory.

The method can also be used to assess the accuracy of gene-editing techniques.

The researchers included scientists from the University of California, Berkeley (UC Berkeley) and the Keck Graduate Institute (KGI) of The Claremont Colleges.

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And HERE …

And watch the promo video HERE …

Is CRISPR a National Security Threat?

National Security Implications of Gene Editing

“CRISPR-Cas9 is here and now, he pointed out. “Gene editing has a number of near term and longer term ramifications that … have implications for national security, intelligence and defense,” he said.

Is CRISPR a National Security Threat?

If the research goes clandestine, the technology could be used to modify various physiological functions in humans both before birth and perhaps key operational points or optimized points after birth, he said.

With genomic knowledge of weaknesses and susceptibilities to certain diseases, populations could be targeted in order to cause instability in societies.”


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One-stop shopping for your gene-editing needs

Brand new CRISPR/Cas9 Platform: One-stop Gene Knockout/knockin Service for Precise Gene Editing

One-stop shopping for your gene-editing needs

New York, Mar 25th, 2019 - Creative Biogene, as a leading provider focuses on offering professional products and services to accelerate gene research, recently announces the brand new CRISPR/Cas9 Platform, which provides comprehensive gene editing services and products. With talented and experienced scientists, Creative Biogene can offer more reliable and professional service to support gene editing projects.

Read the whole press release here …

New CRISPR Diagnostics Firm

Broad, Wyss Institute Researchers Launch CRISPR Dx Firm Sherlock Biosciences

NEW YORK (GenomeWeb) – Engineering biology startup Sherlock Biosciences announced today that it has launched with initial financing of $35 million and licenses to foundational CRISPR and synthetic biology technology from the Broad Institute and Harvard's Office of Technology Development…

Sherlock will use engineering biology tools, including CRISPR and synthetic biology, to develop a new generation of molecular diagnostics that can rapidly deliver accurate results for a vast range of needs in virtually any setting and at low cost, the company said.

The financing includes a $17.5 million non-dilutive grant and an investment from the Open Philanthropy Project, as well as funds from additional undisclosed investors.

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CRISP documentary reviewed in Ars Technica

New documentary has a good time asking how gene editing might change the world

Here's a poorly kept secret: the internal chatter at a given research and scientific institution is typically more interesting than what emerges on the public record. Published papers and newspaper interviews don't come with the banter, pop-culture references, or sheer wit that pumps through most nerds' veins.

CRISP documentary reviewed in Ars Technica

I thought back to all that nerd humor when I reflected on Human Nature, a documentary about gene editing and CRISPR that had its world premiere at South by Southwest 2019. There's a lot of ground to cover on such a topic, and the film, co-produced by Dan Rather, does quite well by identifying existing research and studies, then grounding them with context and equal parts optimism and pessimism. But Human Nature is also the rare science film that isn't afraid to let its smart talking heads be funny, dorky, or just plain sharp.

T-cell modification with CRISPR-Cpf1

Researchers engineer immune cells to fight cancer

T-cell modification with CRISPR-Cpf1

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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Berkeley gets another CRISPR patent

University of California granted another CRISPR patent

UC Berkeley announced Tuesday it received a patent for a single-molecule guide RNA that can be used with the Cas-9 enzyme by the gene-editing tool CRISPR in plants, bacteria and mammalian cells.

Why it matters: Discovering new methods of making CRISPR's gene editing more precise are key to its future success in modifying crops and treating diseases. But, there's also a race among institutions — especially between UC and the Broad Institute — to own CRISPR patents that are potentially worth billions, per Reuters.

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Background: CRISPR can use different enzymes, most often Cas9, to target specific genes for editing, but there remain safety concerns, as it's been shown to sometimes cause unwanted deletions, edit the wrong genes or move genes around. Guide RNAs can be used to locate the proper DNA sequence that needs to be cut.

By the numbers: This is UC Berkeley's third CRISPR patent and they expect a fourth to be issued soon.

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or go even deeper: UC Berkeley team awarded second CRISPR-Cas9 patent

Coverage of the Genome-wide Off-target analysis by Two-cell embryo Injection

A Tool To Validate The Safety Of Gene Editing Systems

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AsianScientist (Mar. 12, 2019) – A team of international scientists has developed a technique to evaluate the safety of genome-editing techniques. The research was published in Science. CRISPR-Cas9 is a new generation of gene-editing tool that has been widely used. However, the risk of off-target effects in vivo, which could lead to diseases such as cancer, remains a serious concern. A variety of off-target detection schemes have been developed, with most relying on the prediction of off-target sites based on sequence similarity or in vitro amplification. However, the latter process may introduce a large amount of noise, thus making it difficult to separate off-target signals from background noise. Whether CRISPR-Cas9 induces off-target effects has been controversial.



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Read the original article at Science

Potential to remove HIV from infected cells

‘Molecular scissors’ successfully remove HIV genes from all tissues in infected monkeys

The top story from the Conference on Retroviruses and Opportunistic Infections (CROI 2019) in Seattle this week has been a likely second HIV cure. However, the cure involved an expensive and risky therapy – a bone-marrow transplant – that would never be broadly applicable.

Just as significant in the long term may be a study reported in the same session that used much more benign technology to achieve what may be a cure in monkeys.

A team of researchers at Temple University in Philadelphia, USA, has removed the retroviral genes from the cells of monkeys infected with SIV, the monkey analogue of HIV. The researchers found that the gene-snipping enzyme they used, contained within the shell of a common cold-type virus so that it could simulate an infection and enter cells, successfully removed the SIV genes from a majority – and possibly all – cells in all the monkeys’ organs where levels were measured, including hard-to-access ones such as the brain.

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Human disease models made in frogs with CRISPR

Modeling human point mutation diseases in Xenopus tropicalis with a modified CRISPR/Cas9 system

Abstract

Xenopus tropicalis with CRISPR. Genome Media

Precise single-base editing in Xenopus tropicalis would greatly expand the utility of this true diploid frog for modeling human genetic diseases caused by point mutations. Here, we report the efficient conversion of C-to-T or G-to-A in X. tropicalis using the rat apolipoprotein B mRNA editing enzyme catalytic subunit 1–XTEN–clustered regularly interspaced short palindromic repeat–associated protein 9 (Cas9) nickase–uracil DNA glycosylase inhibitor–nuclear localization sequence base editor [base editor 3 (BE3)]. Coinjection of guide RNA and the Cas9 mutant complex mRNA into 1-cell stage X. tropicalis embryos caused precise C-to-T or G-to-A substitution in 14 out of 19 tested sites with efficiencies of 5–75%, which allowed for easy establishment of stable lines. Targeting the conserved T-box 5 R237 and Tyr C28 residues in X. tropicalis with the BE3 system mimicked human Holt-Oram syndrome and oculocutaneous albinism type 1A, respectively. Our data indicate that BE3 is an easy and efficient tool for precise base editing in X. tropicalis.—Shi, Z., Xin, H., Tian, D., Lian, J., Wang, J., Liu, G., Ran, R., Shi, S., Zhang, Z., Shi, Y., Deng, Y., Hou, C., Chen, Y. Modeling human point mutation diseases in Xenopus tropicalis with a modified CRISPR/Cas9 system.



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Increasing CRISPR efficiency, and specificity with zinc-finger proteins (original article)

Diversifying the structure of zinc finger nucleases for high-precision genome editing

Increasing CRISPR efficiency, and specificity with zinc-finger proteins. Genome Media.

Abstract—Genome editing for therapeutic applications often requires cleavage within a narrow sequence window. Here, to enable such high-precision targeting with zinc-finger nucleases (ZFNs), we have developed an expanded set of architectures that collectively increase the configurational options available for design by a factor of 64. These new architectures feature the functional attachment of the FokI cleavage domain to the amino terminus of one or both zinc-finger proteins (ZFPs) in the ZFN dimer, as well as the option to skip bases between the target triplets of otherwise adjacent fingers in each zinc-finger array. Using our new architectures, we demonstrate targeting of an arbitrarily chosen 28 bp genomic locus at a density that approaches 1.0 (i.e., efficient ZFNs available for targeting almost every base step). We show that these new architectures may be used for targeting three loci of therapeutic significance with a high degree of precision, efficiency, and specificity.


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CRISPR-based gene therapy, speculating about a time-table

We’re still a long way from using gene-editing for medical conditions?

CRISPR-based gene therapy, speculating about a time-table. Genome Media.

Gene editing has been in the news lately due to an ethically reckless experiment in which human embryos were subjected to an inefficient form of gene editing. The subjects, now born, gained uncertain protection from HIV in exchange for a big collection of potential risks. A large number of ethicists and scientists agreed that this isn't the sort of thing we should be using gene editing for.

Gene editing will likely always come with a bit of risk; when you're cutting and pasting DNA in millions of cells, extremely rare events can't be avoided. So the ethical questions come down to how we can minimize those risks and what conditions make them worth taking.


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