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CRISPR

CRISPR

Clustered regularly interspaced short palindromic repeats (CRISPR) is a prokaryotic adaptive immune response that provides immunity against foreign nucleic acids, such as viral DNA and bacterial plasmids, through the use of crRNAs (CRISPR RNAs) and associated Cas genes.

Clustered regularly interspaced short palindromic repeats (CRISPR) is a prokaryotic adaptive immune response that provides immunity against foreign nucleic acids, particularly viral DNA or RNA, through the use of crRNAs (CRISPR RNAs) and associated Cas genes. 



The CRISPR response evolved to defend bacteria and archaea against infection with bacteriophages, and CRISPR genes are present in the majority of bacterial and archaeal genomes. CRISPR systems share several common features: first, a mechanism for recognition and processing of foreign nucleic acids into short 'spacer' sequences; second, a mechanism for incorporation of these spacers into clusters (CRISPRs) on the bacterial genome, which are regularly interspersed by a short, repeated palindromic DNA sequence; third, a mechanism for transcribing and processing this CRISPR sequence into RNA molecules (known as CRISPR RNAs, or crRNAs) comprising the spacer sequence and a hairpin formed by the palindromic repeat; and finally, recognition and cleavage of DNA or RNA matching the spacer sequence by a protein-RNA complex consisting of both the crRNA and a nuclease. To avoid self-cleavage of the CRISPR locus in the microbe's genome, spacer sequences must occur next to a short DNA sequence, called the Protospacer-Adjacent Motif (PAM), which is not present in the CRISPR locus of the genome. This PAM sequence must be present in order for a spacer to be incorporated into the CRISPR locus, and must be present next to DNA/RNA matching the spacer in order for the crRNA/nuclease complex to recognize and cleave it. The genes and proteins involved with spacer acquisition, crRNA processing, and crRNA-guided cleavage are named CRISPR-Associated (Cas). In type II CRISPR systems, a single gene called Cas9 produces a DNA endonuclease which binds to the crRNA (which, when fused with a trans-activating crRNA, is called a short guide RNA or sgRNA), and can bind and introduce DNA double strand breaks at sequences matching the crRNA's spacer region. The Cas9/sgRNA complex can be programmed to cleave any PAM-adjacent DNA sequence, simply by changing the the spacer (also known as the guide) sequence. Cas nucleases from type V CRISPR systems (such as Cpf1/Cas12A) have also been adapted to programmably cleave DNA, while nucleases from type VI CRISPR systems (such as C2c2/Cas13A) have been adapted to programmably cleave RNA.



CRISPR has been rapidly adopted in biotechnology research as it offers rapid genetic editing at a fraction of the time and cost of previous approaches. Whereas previous gene-editing approaches required protein engineering for each edit, CRISPR can be re-directed to a new site in the genome through supply of a new sgRNA/crRNA complementary to the site of interest. While the first CRISPR variants based around native Cas9 suffered from high off-target mutagenesis rates, protein engineering and the discovery of additional CRISPR variations in bacterial species has led to a rapid proliferation of Cas9-related endonucleases, each with their own benefits and trade-offs. This family of tools is generally referred to as CRISPR. It comprises CRISPRa/CRISPRi acting as artificial transcription factors to regulate gene expression, high-fidelity CRISPR editing tools, drug-inducible endonucleases, molecular imaging tools for DNA binding interactions, and highly sensitive and specific detectors of both DNA and RNA. CRISPR systems are undergoing rapid development worldwide with application to diverse areas such as therapeutics, research tools, and ecological engineering. These developments have highlighted the potential safety issues inherent in a powerful genome editing technology.

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Further reading

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10 High Potential CRISPR Startups to Watch Out In 2018



Article



CRISPR babies: when will the world be ready?



Web

June 19, 2019

Gene-editing tool CRISPR can now manipulate more types of genetic material

The Verge

Article



Will You Eat CRISPR Produce? - NEO.LIFE - Medium

Shelby Pope

Web



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News

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Michael Le Page
February 21, 2020
New Scientist
A genetic tweak can make cells self-destruct in the presence of CRISPR and could be used to make cells tamper-proof or shut them down if they go wrong
Michael Le Page
February 6, 2020
New Scientist
Three people with advanced tumours received a dose of CRISPR gene-edited immune cells and had no serious side effects, paving the way for more trials using this technique
January 30, 2020
WebWire
Mammoth Biosciences, the company behind the world's first CRISPR-based disease detection platform, today announced an oversubscribed round of $45 million in its Series B. The raise is led by Decheng Capital and has participation from Mayfield, NFX, Verily, Brook Byers, Plum Alley, Pacific 8, aMoon, and others. The capital will fuel the company's further development of CRISPR diagnostics and next-generation CRISPR products as it extends its platform to include gene-editing and therapeutics...
Alisa Opar
January 27, 2020
Scientific American
Scientific American is the essential guide to the most awe-inspiring advances in science and technology, explaining how they change our understanding of the world and shape our lives.
Elie Dolgin
January 17, 2020
Scientific American
Scientific American is the essential guide to the most awe-inspiring advances in science and technology, explaining how they change our understanding of the world and shape our lives.
WIRED Staff
December 31, 2019
Wired
The number of satellites in orbit will double. Lots more people will get Crispr'd. Organoids might demand of bill of rights. No big deal!
December 30, 2019
news.google.com
What will people remember about the year 2019 in the year 3019? Just as they're likely to recall 1969 as the year humans first walked on the moon, they might well hold up the first portrait of a black hole as this year's most memorable achievement. By that measure, there's little question
Jessica Hamzelou
December 30, 2019
New Scientist
He Jiankui, the scientist who used CRISPR to create two gene-edited girls born in 2018, has been handed a three-year jail term by a court in Shenzen, China
AFP
December 17, 2019
The Hindu
Here are six major scientific discoveries that shaped the 2010s
December 16, 2019
WebWire
Mammoth Biosciences, the company developing the next generation of CRISPR products, today announced the addition of two key members to its executive team. The expansion of the team supports Mammoth's growth in the life sciences market as the company continues to discover and democratize access to CRISPR systems. Peter Nell, Ph.D. joins Mammoth Biosciences as Chief Business Officer and Head of Therapeutics. In this role, he'll leverage his vast business development and corporate strate...
December 9, 2019
WebWire
Bacteria and the viruses that infect them are engaged in a molecular arms race as ancient as life itself. Evolution has equipped bacteria with an arsenal of immune enzymes, including CRISPR-Cas systems, that target and destroy viral DNA. But bacteria-killing viruses, also known as phages, have devised their own tools to help them outmaneuver even the most formidable of these bacterial defenses. Now, scientists at UC San Francisco and UC San Diego have discovered a remarkable new strategy...
Dan Rather
December 8, 2019
the Guardian
Crispr research: 'It's cheap, it's relatively simple and it's remarkably precise.' Photograph: Bill Oxford/Getty Images/iStockphoto
Peter Bradshaw
December 4, 2019
the Guardian
In the pink ... Human Nature charts the hopes for DNA 'editing'
December 3, 2019
news.yahoo.com
Seattle-based Cyrus Biotechnology says it'll collaborate with the Broad Institute of MIT and Harvard on ways to optimize CRISPR gene-editing techniques for use in developing novel human therapeutics. CRISPR has revolutionized genetics by making it easier to modify the DNA coding in the genome, but
MARILYNN MARCHIONE / AP
November 28, 2019
Time
Chinese scientist He Jiankui shocked the world by claiming he helped make the first gene-edited babies. He has not been seen publicly since January and nothing is known about the health of the babies
Sarah Buhr
November 15, 2019
TechCrunch
CRISPR, the revolutionary ability to snip out and alter genes with scissor-like precision, has exploded in popularity over the last few years and is generally seen as the standalone wizard of modern gene-editing. However, it's not a perfect system, sometimes cutting at the wrong place, not working as intended and leaving scientists scratching their heads. [...]
Associated Press
November 11, 2019
Los Angeles Times
After controversial guidelines were introduced, cholesterol levels are inching down and more Americans are taking much-needed statin drugs.
Associated Press
November 6, 2019
Los Angeles Times
The first attempt in the U.S. to use CRISPR against cancer seems safe in three patients who have had it so far, but it's too soon to know whether it will help.
Diana Gitig
October 30, 2019
Ars Technica
Altering rice genes the pathogen needs renders rice strains resistant to blight.
Dr. Francis S. Collins
October 24, 2019
Time
Our world has never witnessed a time of greater promise for improving human health. But much more remains to be done.
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