Human Papillomavirus Oncogene Manipulation Using Clustered Regularly Interspersed Short Palindromic Repeats/Cas9 Delivered by pH-Sensitive Cationic Liposomes
Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technology enables targeted gene editing, but cancer gene therapy with this approach requires improvements to enable safe and efficient delivery of CRISPR/Cas9 to tumors. We developed and evaluated a...
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| Veröffentlicht in: | Human gene therapy 2020-03, Vol.31 (5-6), p.309-324 |
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| container_title | Human gene therapy |
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| creator | Zhen, Shuai Liu, Yan Lu, Jiaojiao Tuo, Xiaoqian Yang, Xiling Chen, Hong Chen, Wei Li, Xu |
| description | Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technology enables targeted gene editing, but cancer gene therapy with this approach requires improvements to enable safe and efficient delivery of CRISPR/Cas9 to tumors. We developed and evaluated a self-assembled liposome to selectively deliver CRISPR/Cas9 to cancer tissues. Our CRISPR/Cas9 system effectively inhibited proliferation of human papillomavirus (HPV) 16-positive cervical cancer cells and induced apoptosis by inactivating the HR-HPV16E6/E7 oncogene. Based on this system, we prepared a long-circulating pH-sensitive cationic nano-liposome complex with a high cell targeting and gene knockout rate. Intratumoral injection of cationic liposomes targeted to splicing HPV16 E6/E7 in nude mice significantly inhibited tumor growth without significant toxicity
. Liposomes that targeted HPV16 E6/E7 splicing were established as a basis for treatment of HPV16-positive cervical cancer drug candidates. Our study demonstrates that this liposome offers an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine-based cancer therapeutics. |
| doi_str_mv | 10.1089/hum.2019.312 |
| format | Article |
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. Liposomes that targeted HPV16 E6/E7 splicing were established as a basis for treatment of HPV16-positive cervical cancer drug candidates. Our study demonstrates that this liposome offers an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine-based cancer therapeutics.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/hum.2019.312</identifier><identifier>PMID: 31973584</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Apoptosis ; Biocompatibility ; Cancer ; Cations ; Cell proliferation ; Cervical cancer ; Cervix ; CRISPR ; Drug delivery systems ; Drug development ; Gene therapy ; Genetic modification ; Human papillomavirus ; Liposomes ; Oncogenes ; pH effects ; Precision medicine ; Self-assembly ; Splicing ; Toxicity ; Tumors</subject><ispartof>Human gene therapy, 2020-03, Vol.31 (5-6), p.309-324</ispartof><rights>Copyright Mary Ann Liebert, Inc. Mar 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-8453bd9d5c5bcd5140a0835cde7a28706526c439b4eb186b7eadc3a966c6bf033</citedby><cites>FETCH-LOGICAL-c357t-8453bd9d5c5bcd5140a0835cde7a28706526c439b4eb186b7eadc3a966c6bf033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31973584$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhen, Shuai</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Lu, Jiaojiao</creatorcontrib><creatorcontrib>Tuo, Xiaoqian</creatorcontrib><creatorcontrib>Yang, Xiling</creatorcontrib><creatorcontrib>Chen, Hong</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><creatorcontrib>Li, Xu</creatorcontrib><title>Human Papillomavirus Oncogene Manipulation Using Clustered Regularly Interspersed Short Palindromic Repeats/Cas9 Delivered by pH-Sensitive Cationic Liposomes</title><title>Human gene therapy</title><addtitle>Hum Gene Ther</addtitle><description>Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technology enables targeted gene editing, but cancer gene therapy with this approach requires improvements to enable safe and efficient delivery of CRISPR/Cas9 to tumors. We developed and evaluated a self-assembled liposome to selectively deliver CRISPR/Cas9 to cancer tissues. Our CRISPR/Cas9 system effectively inhibited proliferation of human papillomavirus (HPV) 16-positive cervical cancer cells and induced apoptosis by inactivating the HR-HPV16E6/E7 oncogene. Based on this system, we prepared a long-circulating pH-sensitive cationic nano-liposome complex with a high cell targeting and gene knockout rate. Intratumoral injection of cationic liposomes targeted to splicing HPV16 E6/E7 in nude mice significantly inhibited tumor growth without significant toxicity
. Liposomes that targeted HPV16 E6/E7 splicing were established as a basis for treatment of HPV16-positive cervical cancer drug candidates. Our study demonstrates that this liposome offers an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine-based cancer therapeutics.</description><subject>Apoptosis</subject><subject>Biocompatibility</subject><subject>Cancer</subject><subject>Cations</subject><subject>Cell proliferation</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>CRISPR</subject><subject>Drug delivery systems</subject><subject>Drug development</subject><subject>Gene therapy</subject><subject>Genetic modification</subject><subject>Human papillomavirus</subject><subject>Liposomes</subject><subject>Oncogenes</subject><subject>pH effects</subject><subject>Precision medicine</subject><subject>Self-assembly</subject><subject>Splicing</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>1043-0342</issn><issn>1557-7422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpdkc1u1DAURi1ERUthxxpZYsOCTP2fZIlSYCpN1YrSdeQ4d6auHDvYcaV5GN4VT1tYdGHZ-nz8XUsHoQ-UrChp2rO7PK0Yoe2KU_YKnVAp66oWjL0uZyJ4Rbhgx-htSveEUC5V_QYdc9rWXDbiBP1Z50l7fK1n61yY9IONOeErb8IOPOBL7e2cnV5s8Pg2Wb_DnctpgQgj_gm7chXdHl_4kqS5rBLf3IW4lEZn_RjDZE0BZ9BLOut0avE5OPvw-H7Y43ld3YBPdikR7h7HFH5j55DCBOkdOtpql-D9836Kbr9_-9Wtq83Vj4vu66YyXNZL1QjJh7EdpZGDGSUVRJOGSzNCrVlTEyWZMoK3g4CBNmqoQY-G61Ypo4Yt4fwUfX7qnWP4nSEt_WSTAee0h5BTz7gQrFaNOqCfXqD3IUdffleohipZ6lihvjxRJoaUImz7OdpJx31PSX_Q1hdt_UFbX7QV_ONzaR4mGP_D_zzxv5v0lhQ</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>Zhen, Shuai</creator><creator>Liu, Yan</creator><creator>Lu, Jiaojiao</creator><creator>Tuo, Xiaoqian</creator><creator>Yang, Xiling</creator><creator>Chen, Hong</creator><creator>Chen, Wei</creator><creator>Li, Xu</creator><general>Mary Ann Liebert, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>202003</creationdate><title>Human Papillomavirus Oncogene Manipulation Using Clustered Regularly Interspersed Short Palindromic Repeats/Cas9 Delivered by pH-Sensitive Cationic Liposomes</title><author>Zhen, Shuai ; Liu, Yan ; Lu, Jiaojiao ; Tuo, Xiaoqian ; Yang, Xiling ; Chen, Hong ; Chen, Wei ; Li, Xu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-8453bd9d5c5bcd5140a0835cde7a28706526c439b4eb186b7eadc3a966c6bf033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Apoptosis</topic><topic>Biocompatibility</topic><topic>Cancer</topic><topic>Cations</topic><topic>Cell proliferation</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>CRISPR</topic><topic>Drug delivery systems</topic><topic>Drug development</topic><topic>Gene therapy</topic><topic>Genetic modification</topic><topic>Human papillomavirus</topic><topic>Liposomes</topic><topic>Oncogenes</topic><topic>pH effects</topic><topic>Precision medicine</topic><topic>Self-assembly</topic><topic>Splicing</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhen, Shuai</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Lu, Jiaojiao</creatorcontrib><creatorcontrib>Tuo, Xiaoqian</creatorcontrib><creatorcontrib>Yang, Xiling</creatorcontrib><creatorcontrib>Chen, Hong</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><creatorcontrib>Li, Xu</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology 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>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhen, Shuai</au><au>Liu, Yan</au><au>Lu, Jiaojiao</au><au>Tuo, Xiaoqian</au><au>Yang, Xiling</au><au>Chen, Hong</au><au>Chen, Wei</au><au>Li, Xu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Papillomavirus Oncogene Manipulation Using Clustered Regularly Interspersed Short Palindromic Repeats/Cas9 Delivered by pH-Sensitive Cationic Liposomes</atitle><jtitle>Human gene therapy</jtitle><addtitle>Hum Gene Ther</addtitle><date>2020-03</date><risdate>2020</risdate><volume>31</volume><issue>5-6</issue><spage>309</spage><epage>324</epage><pages>309-324</pages><issn>1043-0342</issn><eissn>1557-7422</eissn><abstract>Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technology enables targeted gene editing, but cancer gene therapy with this approach requires improvements to enable safe and efficient delivery of CRISPR/Cas9 to tumors. We developed and evaluated a self-assembled liposome to selectively deliver CRISPR/Cas9 to cancer tissues. Our CRISPR/Cas9 system effectively inhibited proliferation of human papillomavirus (HPV) 16-positive cervical cancer cells and induced apoptosis by inactivating the HR-HPV16E6/E7 oncogene. Based on this system, we prepared a long-circulating pH-sensitive cationic nano-liposome complex with a high cell targeting and gene knockout rate. Intratumoral injection of cationic liposomes targeted to splicing HPV16 E6/E7 in nude mice significantly inhibited tumor growth without significant toxicity
. Liposomes that targeted HPV16 E6/E7 splicing were established as a basis for treatment of HPV16-positive cervical cancer drug candidates. Our study demonstrates that this liposome offers an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine-based cancer therapeutics.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>31973584</pmid><doi>10.1089/hum.2019.312</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Biocompatibility Cancer Cations Cell proliferation Cervical cancer Cervix CRISPR Drug delivery systems Drug development Gene therapy Genetic modification Human papillomavirus Liposomes Oncogenes pH effects Precision medicine Self-assembly Splicing Toxicity Tumors |
| title | Human Papillomavirus Oncogene Manipulation Using Clustered Regularly Interspersed Short Palindromic Repeats/Cas9 Delivered by pH-Sensitive Cationic Liposomes |
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