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CRISPR

Posted by on December 16, 2016 7:41 AM
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CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeat. The functions of CRISPR are essential in adaptive immunity, enabling organisms to respond to and eliminate genetic material.

CRISPR (Wikipedia)
Diagram of the CRISPR prokaryotic antiviral defense mechanism.

Clustered regularly interspaced short palindromic repeats (CRISPR, pronounced crisper) are segments of prokaryotic DNA containing short repetitions of base sequences. Each repetition is followed by short segments of "spacer DNA" from previous exposures to foreign DNA (e.g a virus or plasmid).

The CRISPR/Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements such as those present within plasmids and phages, and provides a form of acquired immunity. CRISPR associated proteins (Cas) use the CRISPR spacers to recognize and cut these exogenous genetic elements in a manner analogous to RNA interference in eukaryotic organisms. CRISPRs are found in approximately 40% of sequenced bacterial genomes and 90% of sequenced archaea.

Cas9 was the first nuclease discovered, followed by Cpf1, which was discovered in the CRISPR/Cpf1 system of Francisella novicida. Other such systems are thought to exist. CRISPR/C2c2 from the bacterium Leptotrichia shahii is RNA-guided CRISPR system that targets RNA rather than DNA, and can either cleave single-stranded RNA targets or knock them down.

By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added. The Cas9-gRNA complex corresponds with the CAS III crRNA complex in the above diagram. CRISPR/Cas genome editing techniques have many potential applications, including altering the germline of humans, animals, and food crops. The use of CRISPR Cas9-gRNA complex for genome editing was the AAAS's choice for breakthrough of the year in 2015.Bioethical concerns have been expressed about the prospect of using this nascent biotechnology for editing the human germline.

Cascade (CRISPR-associated complex for antiviral defense)
CAS 4qyz.png
Structure of crRNA-guided E. coli Cascade complex (Cas, blue) bound to single-stranded DNA (orange).
Identifiers
Organism Escherichia coli
Symbol ?
PDB 4QYZ


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