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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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Annalee Armstrong
September 17, 2021
FierceBiotech
A CRISPR-Cas9 gene editing technology that has shown promise in clearing HIV from mice is headed into human testing. Excision BioTherapeutics will usher the CRISPR-based therapy EBT-101 into clinical trials after the FDA cleared an investigational new drug application.
Emma Betuel
September 13, 2021
TechCrunch
There are a growing number of companies interested in CRISPR's potential to upend medicine. It's probably safe to say there's only one company interested in using the gene-editing system to create a living, breathing woolly mammoth. Or, at least, something pretty close to it. That's the primary mission of a new company called Colossal. Co-founded [...]
Joanna Thompson
September 13, 2021
HowStuffWorks
CRISPR is the genius behind innovations that seemed impossible a decade ago. Could you grow tomatoes with the kick of hot sauce or ferment wine that doesn't cause a hangover? That's just two of the things scientists are looking into.
Gené Teare
September 9, 2021
Crunchbase News
San Francisco-based Mammoth Biosciences has closed on a $150 million Series D led by Redmile Group, which now values the CRISPR biotech company at $1 billion, making it a new addition to the Crunchbase Unicorn Board.
Emma Betuel
September 9, 2021
TechCrunch
The CRISPR-based biotech startup Mammoth Biosciences is officially a unicorn, the company says. The billion dollar valuation comes on the back of a $150 million series D round led by Redmile Group, with participation from Foresite Capital, Senator Investment Group, Sixth Street, Greenspring Associates, Mayfield, Decheng Capital, Plum Alley and NFX. Combined with a late [...]
Amirah Al Idrus
September 9, 2021
FierceBiotech
On the back of a busy year, Mammoth Biosciences is getting a $195 million boost, which will ramp up the development of its gene-editing pipeline, as well as fuel its work in CRISPR-based diagnostics.
Joe Pinkstone
September 3, 2021
The Telegraph
Crispr has enormous potential as a treatment, but one issue holding it back is that it is too big to be easily packaged, limiting its uses
Conor Hale
August 26, 2021
FierceBiotech
Developed by BD in collaboration with Scanwell Health, the Veritor rapid antigen test operates similar to a home pregnancy test, at first.
Arlene Weintraub
August 23, 2021
FierceBiotech
Using CRISPR, a team at Penn's medical school discovered that an epigenetic regulatory protein called ZMYND8 governs the expression of genes that are critical for the growth and survival of AML cells. They uncovered a way to target it with drugs and to predict which patients are likely to respond to ZMYND8 inhibition.
Angus Liu
August 18, 2021
FierceBiotech
COVID-19 mRNA vaccines and existing gene therapies, including those built with the CRISPR-Cas9 gene-editing tool, are delivered into cells with viral vectors or lipid nanoparticles. A research team led by CRISPR pioneer Feng Zhang of the Broad Institute has developed a new mRNA delivery system that harnesses a human protein called PEG10.
Science X staff
August 19, 2021
phys.org
Zebrafish--small, fast-growing creatures who share many of the same genes as humans--are instrumental to many biologists, who find them uniquely well suited for studying a wide range of questions, from how organisms develop to how the nervous system drives behavior. Now, with a new technology developed by University of Utah Health scientists called MIC-Drop, the fish will be even more powerful for large-scale genetic studies.
Science X staff
August 18, 2021
phys.org
Studying DNA repair is key to future space exploration, which could expose humans to risk of DNA damage caused by radiation. Conditions in space also could affect the way the body repairs such damage, potentially compounding that risk.
IANS
August 16, 2021
News18
Researchers at the Harvard Medical School and Brigham and Women's Hospital, Boston, have called this technique 'PICASSO', short for peptide immobilisation by Cas9-mediated self-organisation.
Science X staff
August 13, 2021
phys.org
Scientists have repurposed the genetic modification technology CRISPR to identify antibodies in patient blood samples in a move that could inspire a new class of medical diagnostics in addition to a host of other applications.
Naveen
August 6, 2021
news.google.com
Research aims to use two CRISPR enzymes to diagnose COVID in 20 minutes
August 6, 2021
Hindustan Times
The new technique, however, is not able to rival the sensitivity of RT-PCR but is at a stage where it can detect just a few copies of the virus per microliter of liquid. Currently, it is able to detect 30 copies per microliter -- sufficient to be used to survey people and limit spread of infections.
Marc Zimmer
August 6, 2021
phys.org
Watson and Crick, Schrödinger and Einstein all made theoretical breakthroughs that have changed the world's understanding of science.
August 6, 2021
ANI News
California [US], August 6 (ANI): A research team led by scientists at the University of California, Berkeley, is aiming to develop a diagnostic test that is much faster and easier to deploy than the RT-PCR test which is today's gold standard for detecting COVID-19.
Science X staff
August 3, 2021
phys.org
In the latest of ongoing efforts to expand technologies for modifying genes and their expression, researchers in the lab of Neville Sanjana at New York University (NYU) and the New York Genome Center (NYGC) have developed chemically modified guide RNAs for a CRISPR system that targets RNA instead of DNA. These chemically modified guide RNAs significantly enhance the ability to target--trace, edit, and/or knockdown--RNA in human cells.
Jamie Ducharme
August 2, 2021
Time
MRNA, the genetic material used in Pfizer and Moderna's COVID-19 vaccines, could also be used to create a new class of drugs and therapies.
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