CRISPR Cas9 in Genome Editing and Beyond
The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily prog...
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Veröffentlicht in: | Annual review of biochemistry 2016-06, Vol.85 (1), p.227-264 |
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description | The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR Cas9 technology offers. |
doi_str_mv | 10.1146/annurev-biochem-060815-014607 |
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As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR Cas9 technology offers.</description><identifier>ISSN: 0066-4154</identifier><identifier>EISSN: 1545-4509</identifier><identifier>DOI: 10.1146/annurev-biochem-060815-014607</identifier><identifier>PMID: 27145843</identifier><identifier>CODEN: ARBOAW</identifier><language>eng</language><publisher>United States: Annual Reviews</publisher><subject>Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Base Pairing ; Biochemistry ; Cas9 structure ; Clustered Regularly Interspaced Short Palindromic Repeats ; CRISPR applications ; CRISPR-Associated Protein 9 ; CRISPR-Cas Systems ; dCas9 ; Deoxyribonucleic acid ; DNA ; DNA Cleavage ; DNA Repair ; Endonucleases - genetics ; Endonucleases - metabolism ; Epigenesis, Genetic ; epigenetic regulation ; Epigenetics ; Gene Editing - methods ; gene regulation ; Gene Targeting ; Genome, Human ; Genomes ; genomic imaging ; Humans ; Immune system ; Molecular Imaging ; Protein Engineering ; Protein Structure, Secondary ; Proteins ; Ribonucleic acid ; RNA ; RNA, Guide, CRISPR-Cas Systems - genetics ; RNA, Guide, CRISPR-Cas Systems - metabolism</subject><ispartof>Annual review of biochemistry, 2016-06, Vol.85 (1), p.227-264</ispartof><rights>Copyright © 2016 by Annual Reviews. All rights reserved 2016</rights><rights>Copyright Annual Reviews, Inc. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a626t-d99c66c7bc510b3333d4ee793ad8dcfe59ef6482217c57720d86680c9a3a99313</citedby><cites>FETCH-LOGICAL-a626t-d99c66c7bc510b3333d4ee793ad8dcfe59ef6482217c57720d86680c9a3a99313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.annualreviews.org/content/journals/10.1146/annurev-biochem-060815-014607?crawler=true&mimetype=application/pdf$$EPDF$$P50$$Gannualreviews$$H</linktopdf><linktohtml>$$Uhttps://www.annualreviews.org/content/journals/10.1146/annurev-biochem-060815-014607$$EHTML$$P50$$Gannualreviews$$H</linktohtml><link.rule.ids>70,314,776,780,4168,27901,27902,77997,77998</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27145843$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Haifeng</creatorcontrib><creatorcontrib>La Russa, Marie</creatorcontrib><creatorcontrib>Qi, Lei S</creatorcontrib><title>CRISPR Cas9 in Genome Editing and Beyond</title><title>Annual review of biochemistry</title><addtitle>Annu Rev Biochem</addtitle><description>The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR Cas9 technology offers.</description><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Base Pairing</subject><subject>Biochemistry</subject><subject>Cas9 structure</subject><subject>Clustered Regularly Interspaced Short Palindromic Repeats</subject><subject>CRISPR applications</subject><subject>CRISPR-Associated Protein 9</subject><subject>CRISPR-Cas Systems</subject><subject>dCas9</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Cleavage</subject><subject>DNA Repair</subject><subject>Endonucleases - genetics</subject><subject>Endonucleases - metabolism</subject><subject>Epigenesis, Genetic</subject><subject>epigenetic regulation</subject><subject>Epigenetics</subject><subject>Gene Editing - methods</subject><subject>gene regulation</subject><subject>Gene Targeting</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>genomic imaging</subject><subject>Humans</subject><subject>Immune system</subject><subject>Molecular Imaging</subject><subject>Protein Engineering</subject><subject>Protein Structure, Secondary</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Guide, CRISPR-Cas Systems - genetics</subject><subject>RNA, Guide, CRISPR-Cas Systems - metabolism</subject><issn>0066-4154</issn><issn>1545-4509</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE1LAzEQhoMotlb_giyI0MvqZPO1OXiwpdZCQal6DmmS6pZutm66Sv-9KVs9eBFzGcg88w7zIHSJ4Qpjyq-1903tPtJ5UZk3V6bAIccshdgDcYC6mFGWUgbyEHUBOE9p_OmgkxCWAEAkzY5RJxOYspySLuoPZ5Onx1ky1EEmhU_GzlelS0a22BT-NdHeJgO3rbw9RUcLvQrubF976OVu9Dy8T6cP48nwdppqnvFNaqU0nBsxNwzDnMRnqXNCEm1zaxaOSbfgNM8yLAwTIgObc56DkZpoKQkmPdRvc9d19d64sFFlEYxbrbR3VRMUzjHOJcNE_o0KKTLCiGARvfiFLqum9vGQHSUh40B4pG5aytRVCLVbqHVdlLreKgxqZ1_t7au9fdXaV639OH--39LMS2d_pr91R2DQArscvYpJhfsM_9zyBV_pl8k</recordid><startdate>20160602</startdate><enddate>20160602</enddate><creator>Wang, Haifeng</creator><creator>La Russa, Marie</creator><creator>Qi, Lei S</creator><general>Annual Reviews</general><general>Annual Reviews, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20160602</creationdate><title>CRISPR Cas9 in Genome Editing and Beyond</title><author>Wang, Haifeng ; La Russa, Marie ; Qi, Lei S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a626t-d99c66c7bc510b3333d4ee793ad8dcfe59ef6482217c57720d86680c9a3a99313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Base Pairing</topic><topic>Biochemistry</topic><topic>Cas9 structure</topic><topic>Clustered Regularly Interspaced Short Palindromic Repeats</topic><topic>CRISPR applications</topic><topic>CRISPR-Associated Protein 9</topic><topic>CRISPR-Cas Systems</topic><topic>dCas9</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Cleavage</topic><topic>DNA Repair</topic><topic>Endonucleases - genetics</topic><topic>Endonucleases - metabolism</topic><topic>Epigenesis, Genetic</topic><topic>epigenetic regulation</topic><topic>Epigenetics</topic><topic>Gene Editing - methods</topic><topic>gene regulation</topic><topic>Gene Targeting</topic><topic>Genome, Human</topic><topic>Genomes</topic><topic>genomic imaging</topic><topic>Humans</topic><topic>Immune system</topic><topic>Molecular Imaging</topic><topic>Protein Engineering</topic><topic>Protein Structure, Secondary</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Guide, CRISPR-Cas Systems - genetics</topic><topic>RNA, Guide, CRISPR-Cas Systems - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Haifeng</creatorcontrib><creatorcontrib>La Russa, Marie</creatorcontrib><creatorcontrib>Qi, Lei S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Annual review of biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Haifeng</au><au>La Russa, Marie</au><au>Qi, Lei S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CRISPR Cas9 in Genome Editing and Beyond</atitle><jtitle>Annual review of biochemistry</jtitle><addtitle>Annu Rev Biochem</addtitle><date>2016-06-02</date><risdate>2016</risdate><volume>85</volume><issue>1</issue><spage>227</spage><epage>264</epage><pages>227-264</pages><issn>0066-4154</issn><eissn>1545-4509</eissn><coden>ARBOAW</coden><abstract>The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. 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subjects | Bacterial Proteins - genetics Bacterial Proteins - metabolism Base Pairing Biochemistry Cas9 structure Clustered Regularly Interspaced Short Palindromic Repeats CRISPR applications CRISPR-Associated Protein 9 CRISPR-Cas Systems dCas9 Deoxyribonucleic acid DNA DNA Cleavage DNA Repair Endonucleases - genetics Endonucleases - metabolism Epigenesis, Genetic epigenetic regulation Epigenetics Gene Editing - methods gene regulation Gene Targeting Genome, Human Genomes genomic imaging Humans Immune system Molecular Imaging Protein Engineering Protein Structure, Secondary Proteins Ribonucleic acid RNA RNA, Guide, CRISPR-Cas Systems - genetics RNA, Guide, CRISPR-Cas Systems - metabolism |
title | CRISPR Cas9 in Genome Editing and Beyond |
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