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CRISPRs (clustered regularly interspaced short palindromic repeats) 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 a bacterial virus or plasmid.〔 〕 It is pronounced "''crisper''". The CRISPR/Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements such as plasmids and phages,〔 〕 and provides a form of acquired immunity. CRISPR spacers recognize and cut these exogenous genetic elements in a manner analogous to RNAi in eukaryotic organisms.〔 CRISPRs are found in approximately 40% of sequenced bacteria genomes and 90% of sequenced archaea.〔71/79 Archaea, 463/1008 Bacteria (CRISPRdb ), Date: 19.6.2010〕 The CRISPR/Cas system has been used for gene editing (adding, disrupting or changing the sequence of specific genes) and gene regulation in species throughout the tree of life. By delivering the Cas9 protein and appropriate guide RNAs into a cell, the organism's genome can be relatively cheaply cut at any desired location.〔〔〔 〕 CRISPR has a number of potential applications including treating genetic diseases, fighting infections, and increasing food crop yields, but the application of this method is accompanied by ethical concerns. == History == CRISPR is part of a normally occurring bacterial process, though it has only recently been studied, as bacteria may incorporate foreign DNA in other circumstances and even scavenge damaged DNA from their environment. Clustered repeats were first described in 1987 for the bacterium ''Escherichia coli'' by Yoshizumi Ishino, but at that time their function was not known. In 2000, similar repeats were identified in other bacteria and archaea, and were termed Short Regularly Spaced Repeats (SRSR). SRSR were renamed CRISPR in 2002. A set of genes was found to be associated with CRISPR repeats, and was named the ''cas'', or ''CRISPR-associated'', genes. The ''cas'' genes encode putative nuclease or helicase proteins, which are enzymes that can cut DNA.〔 In 2005, three independent research groups showed that some CRISPR spacers are derived from phage DNA and extrachromosomal DNA such as plasmids.〔〔 In effect, the spacers are fragments of DNA gathered from viruses that have previously tried to attack the cell. The source of the spacers was a sign that the CRISPR/cas system could have a role in adaptive immunity in bacteria.〔 Koonin and colleagues proposed that spacers serve as a template for RNA molecules, analogous to a system called RNA interference used by eukaryotic cells. In 2007, Barrangou, Horvath (food industry scientists at Danisco) and Moineau's group at Université Laval (Canada) showed that they could use spacer DNA to alter the resistance of ''Streptococcus thermophilus'' to phage attack.〔 Doudna and Charpentier had independently been exploring CRISPR-associated proteins to learn how bacteria use spacers in their immune defenses. They jointly studied a simpler CRISPR system that relies on a protein called Cas9. They found that bacteria respond to an invading phage by transcribing spacers and palindromic DNA into a long RNA molecule. The cell then uses tracrRNA and Cas9 to cut this long RNA molecule into pieces called crRNAs.〔 Cas9 is a nuclease, an enzyme specialized for cutting DNA. It has two active cutting sites (HNH and RuvC), one for each strand of the DNA's double helix. The team demonstrated that they could disable one or both sites while preserving Cas9's ability to home in on its target DNA. Jinek combined tracrRNA and spacer RNA into a "single-guide RNA" molecule that, mixed with Cas9, could find and cut the correct DNA targets. Jinek ''et al'' proposed that such synthetic guide RNAs could be used for gene editing.〔 CRISPR was first shown to work as a genome engineering/editing tool in human cell culture by 2012.〔 It has since been used in a wide range of organisms including baker's yeast (''S. cerevisiae''), zebrafish (''D. rerio''), flies (''D. melanogaster''), axolotl (''A. mexicanum''), nematodes (''C. elegans''), plants, mice, monkeys, nonviable human embryos〔 and other organisms. Additionally CRISPR has been modified to make programmable transcription factors that allow scientists to target and activate or silence specific genes. Libraries of tens of thousands of guide RNAs are available.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「CRISPR」の詳細全文を読む スポンサード リンク
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