Correction of recessive dystrophic epidermolysis bullosa by homology-directed repair-mediated genome editing
Genome-editing technologies that enable the introduction of precise changes in DNA sequences have the potential to lead to a new class of treatments for genetic diseases. Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by extreme skin fragility. The recessive dystrophic...
Gespeichert in:
| Veröffentlicht in: | Molecular therapy 2021-06, Vol.29 (6), p.2008-2018 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2018 |
|---|---|
| container_issue | 6 |
| container_start_page | 2008 |
| container_title | Molecular therapy |
| container_volume | 29 |
| creator | Bonafont, Jose Mencía, Angeles Chacón-Solano, Esteban Srifa, Wai Vaidyanathan, Sriram Romano, Rosa Garcia, Marta Hervás-Salcedo, Rosario Ugalde, Laura Duarte, Blanca Porteus, Matthew H. Del Rio, Marcela Larcher, Fernando Murillas, Rodolfo |
| description | Genome-editing technologies that enable the introduction of precise changes in DNA sequences have the potential to lead to a new class of treatments for genetic diseases. Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by extreme skin fragility. The recessive dystrophic subtype of EB (RDEB), which has one of the most severe phenotypes, is caused by mutations in COL7A1. In this study, we report a gene-editing approach for ex vivo homology-directed repair (HDR)-based gene correction that uses the CRISPR-Cas9 system delivered as a ribonucleoprotein (RNP) complex in combination with donor DNA templates delivered by adeno-associated viral vectors (AAVs). We demonstrate sufficient mutation correction frequencies to achieve therapeutic benefit in primary RDEB keratinocytes containing different COL7A1 mutations as well as efficient HDR-mediated COL7A1 modification in healthy cord blood-derived CD34+ cells and mesenchymal stem cells (MSCs). These results are a proof of concept for HDR-mediated gene correction in different cell types with therapeutic potential for RDEB.
[Display omitted]
By using CRISPR-Cas9 delivered as a ribonucleoprotein complex in combination with donor DNA templates delivered by adeno-associated viral vectors, Bonafont and colleagues describe highly efficient HDR-mediated gene correction in recessive dystrophic epidermolysis bullosa patient cells. This advanced therapy method opens the way to genome-editing treatments for genetic skin disease. |
| doi_str_mv | 10.1016/j.ymthe.2021.02.019 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8178438</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1525001621000861</els_id><sourcerecordid>2491950673</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-ecf80419c0655915bbae97f253b3f62ac047487f5a42d5583c2e142896c5488f3</originalsourceid><addsrcrecordid>eNp9Uctu2zAQJIIEder2CwIEOuYilU-JPLRAYPQFGMilPRMUtbJpSKJCygb096Fr10guOXF2OTO72EHojuCCYFJ-2RVzP22hoJiSAtMCE3WFbomgIseY8usLJuUCfYxxlxARqvyAFoyVWFWM36Ju5UMAOzk_ZL7NEoQY3QGyZo5T8OPW2QxG10DofTdHF7N633U-mqyes61PTb-Z88YdPaBJ-tG4kPfQOHOsNzD4HrJUTm7YfEI3rekifD6_S_T3x_c_q1_5-unn79XjOrdcqCkH20rMibK4FEIRUdcGVNVSwWrWltRYzCsuq1YYThshJLMUCKdSlVZwKVu2RN9OvuO-TqtYGKZgOj0G15swa2-cfvszuK3e-IOWpJKcyWTwcDYI_nkPcdK9ixa6zgzg91FTrogSuKxYorIT1QYfY4D2MoZgfcxJ7_S_nPQxJ42pTjkl1f3rDS-a_8EkwtcTAdKdDg6CjtbBYOF0at149-6AF5xmqKY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2491950673</pqid></control><display><type>article</type><title>Correction of recessive dystrophic epidermolysis bullosa by homology-directed repair-mediated genome editing</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Bonafont, Jose ; Mencía, Angeles ; Chacón-Solano, Esteban ; Srifa, Wai ; Vaidyanathan, Sriram ; Romano, Rosa ; Garcia, Marta ; Hervás-Salcedo, Rosario ; Ugalde, Laura ; Duarte, Blanca ; Porteus, Matthew H. ; Del Rio, Marcela ; Larcher, Fernando ; Murillas, Rodolfo</creator><creatorcontrib>Bonafont, Jose ; Mencía, Angeles ; Chacón-Solano, Esteban ; Srifa, Wai ; Vaidyanathan, Sriram ; Romano, Rosa ; Garcia, Marta ; Hervás-Salcedo, Rosario ; Ugalde, Laura ; Duarte, Blanca ; Porteus, Matthew H. ; Del Rio, Marcela ; Larcher, Fernando ; Murillas, Rodolfo</creatorcontrib><description>Genome-editing technologies that enable the introduction of precise changes in DNA sequences have the potential to lead to a new class of treatments for genetic diseases. Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by extreme skin fragility. The recessive dystrophic subtype of EB (RDEB), which has one of the most severe phenotypes, is caused by mutations in COL7A1. In this study, we report a gene-editing approach for ex vivo homology-directed repair (HDR)-based gene correction that uses the CRISPR-Cas9 system delivered as a ribonucleoprotein (RNP) complex in combination with donor DNA templates delivered by adeno-associated viral vectors (AAVs). We demonstrate sufficient mutation correction frequencies to achieve therapeutic benefit in primary RDEB keratinocytes containing different COL7A1 mutations as well as efficient HDR-mediated COL7A1 modification in healthy cord blood-derived CD34+ cells and mesenchymal stem cells (MSCs). These results are a proof of concept for HDR-mediated gene correction in different cell types with therapeutic potential for RDEB.
[Display omitted]
By using CRISPR-Cas9 delivered as a ribonucleoprotein complex in combination with donor DNA templates delivered by adeno-associated viral vectors, Bonafont and colleagues describe highly efficient HDR-mediated gene correction in recessive dystrophic epidermolysis bullosa patient cells. This advanced therapy method opens the way to genome-editing treatments for genetic skin disease.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1016/j.ymthe.2021.02.019</identifier><identifier>PMID: 33609734</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>AAV ; Cell Line ; Collagen Type VII - genetics ; CRISPR ; CRISPR-Cas Systems ; Dependovirus - genetics ; epidermolysis ; Epidermolysis Bullosa Dystrophica - genetics ; Epidermolysis Bullosa Dystrophica - therapy ; Gene Editing - methods ; Gene Expression ; gene therapy ; Gene Transfer Techniques ; Genes, Recessive ; Genetic Therapy - methods ; Genetic Vectors - genetics ; genome editing ; HDR ; Humans ; Keratinocytes - metabolism ; Mutation ; Original ; RDEB ; Recombinational DNA Repair ; skin</subject><ispartof>Molecular therapy, 2021-06, Vol.29 (6), p.2008-2018</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><rights>2021 The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-ecf80419c0655915bbae97f253b3f62ac047487f5a42d5583c2e142896c5488f3</citedby><cites>FETCH-LOGICAL-c459t-ecf80419c0655915bbae97f253b3f62ac047487f5a42d5583c2e142896c5488f3</cites><orcidid>0000-0002-6771-3561</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178438/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178438/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33609734$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bonafont, Jose</creatorcontrib><creatorcontrib>Mencía, Angeles</creatorcontrib><creatorcontrib>Chacón-Solano, Esteban</creatorcontrib><creatorcontrib>Srifa, Wai</creatorcontrib><creatorcontrib>Vaidyanathan, Sriram</creatorcontrib><creatorcontrib>Romano, Rosa</creatorcontrib><creatorcontrib>Garcia, Marta</creatorcontrib><creatorcontrib>Hervás-Salcedo, Rosario</creatorcontrib><creatorcontrib>Ugalde, Laura</creatorcontrib><creatorcontrib>Duarte, Blanca</creatorcontrib><creatorcontrib>Porteus, Matthew H.</creatorcontrib><creatorcontrib>Del Rio, Marcela</creatorcontrib><creatorcontrib>Larcher, Fernando</creatorcontrib><creatorcontrib>Murillas, Rodolfo</creatorcontrib><title>Correction of recessive dystrophic epidermolysis bullosa by homology-directed repair-mediated genome editing</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>Genome-editing technologies that enable the introduction of precise changes in DNA sequences have the potential to lead to a new class of treatments for genetic diseases. Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by extreme skin fragility. The recessive dystrophic subtype of EB (RDEB), which has one of the most severe phenotypes, is caused by mutations in COL7A1. In this study, we report a gene-editing approach for ex vivo homology-directed repair (HDR)-based gene correction that uses the CRISPR-Cas9 system delivered as a ribonucleoprotein (RNP) complex in combination with donor DNA templates delivered by adeno-associated viral vectors (AAVs). We demonstrate sufficient mutation correction frequencies to achieve therapeutic benefit in primary RDEB keratinocytes containing different COL7A1 mutations as well as efficient HDR-mediated COL7A1 modification in healthy cord blood-derived CD34+ cells and mesenchymal stem cells (MSCs). These results are a proof of concept for HDR-mediated gene correction in different cell types with therapeutic potential for RDEB.
[Display omitted]
By using CRISPR-Cas9 delivered as a ribonucleoprotein complex in combination with donor DNA templates delivered by adeno-associated viral vectors, Bonafont and colleagues describe highly efficient HDR-mediated gene correction in recessive dystrophic epidermolysis bullosa patient cells. This advanced therapy method opens the way to genome-editing treatments for genetic skin disease.</description><subject>AAV</subject><subject>Cell Line</subject><subject>Collagen Type VII - genetics</subject><subject>CRISPR</subject><subject>CRISPR-Cas Systems</subject><subject>Dependovirus - genetics</subject><subject>epidermolysis</subject><subject>Epidermolysis Bullosa Dystrophica - genetics</subject><subject>Epidermolysis Bullosa Dystrophica - therapy</subject><subject>Gene Editing - methods</subject><subject>Gene Expression</subject><subject>gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genes, Recessive</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - genetics</subject><subject>genome editing</subject><subject>HDR</subject><subject>Humans</subject><subject>Keratinocytes - metabolism</subject><subject>Mutation</subject><subject>Original</subject><subject>RDEB</subject><subject>Recombinational DNA Repair</subject><subject>skin</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctu2zAQJIIEder2CwIEOuYilU-JPLRAYPQFGMilPRMUtbJpSKJCygb096Fr10guOXF2OTO72EHojuCCYFJ-2RVzP22hoJiSAtMCE3WFbomgIseY8usLJuUCfYxxlxARqvyAFoyVWFWM36Ju5UMAOzk_ZL7NEoQY3QGyZo5T8OPW2QxG10DofTdHF7N633U-mqyes61PTb-Z88YdPaBJ-tG4kPfQOHOsNzD4HrJUTm7YfEI3rekifD6_S_T3x_c_q1_5-unn79XjOrdcqCkH20rMibK4FEIRUdcGVNVSwWrWltRYzCsuq1YYThshJLMUCKdSlVZwKVu2RN9OvuO-TqtYGKZgOj0G15swa2-cfvszuK3e-IOWpJKcyWTwcDYI_nkPcdK9ixa6zgzg91FTrogSuKxYorIT1QYfY4D2MoZgfcxJ7_S_nPQxJ42pTjkl1f3rDS-a_8EkwtcTAdKdDg6CjtbBYOF0at149-6AF5xmqKY</recordid><startdate>20210602</startdate><enddate>20210602</enddate><creator>Bonafont, Jose</creator><creator>Mencía, Angeles</creator><creator>Chacón-Solano, Esteban</creator><creator>Srifa, Wai</creator><creator>Vaidyanathan, Sriram</creator><creator>Romano, Rosa</creator><creator>Garcia, Marta</creator><creator>Hervás-Salcedo, Rosario</creator><creator>Ugalde, Laura</creator><creator>Duarte, Blanca</creator><creator>Porteus, Matthew H.</creator><creator>Del Rio, Marcela</creator><creator>Larcher, Fernando</creator><creator>Murillas, Rodolfo</creator><general>Elsevier Inc</general><general>American Society of Gene & Cell Therapy</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6771-3561</orcidid></search><sort><creationdate>20210602</creationdate><title>Correction of recessive dystrophic epidermolysis bullosa by homology-directed repair-mediated genome editing</title><author>Bonafont, Jose ; Mencía, Angeles ; Chacón-Solano, Esteban ; Srifa, Wai ; Vaidyanathan, Sriram ; Romano, Rosa ; Garcia, Marta ; Hervás-Salcedo, Rosario ; Ugalde, Laura ; Duarte, Blanca ; Porteus, Matthew H. ; Del Rio, Marcela ; Larcher, Fernando ; Murillas, Rodolfo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-ecf80419c0655915bbae97f253b3f62ac047487f5a42d5583c2e142896c5488f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>AAV</topic><topic>Cell Line</topic><topic>Collagen Type VII - genetics</topic><topic>CRISPR</topic><topic>CRISPR-Cas Systems</topic><topic>Dependovirus - genetics</topic><topic>epidermolysis</topic><topic>Epidermolysis Bullosa Dystrophica - genetics</topic><topic>Epidermolysis Bullosa Dystrophica - therapy</topic><topic>Gene Editing - methods</topic><topic>Gene Expression</topic><topic>gene therapy</topic><topic>Gene Transfer Techniques</topic><topic>Genes, Recessive</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors - genetics</topic><topic>genome editing</topic><topic>HDR</topic><topic>Humans</topic><topic>Keratinocytes - metabolism</topic><topic>Mutation</topic><topic>Original</topic><topic>RDEB</topic><topic>Recombinational DNA Repair</topic><topic>skin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bonafont, Jose</creatorcontrib><creatorcontrib>Mencía, Angeles</creatorcontrib><creatorcontrib>Chacón-Solano, Esteban</creatorcontrib><creatorcontrib>Srifa, Wai</creatorcontrib><creatorcontrib>Vaidyanathan, Sriram</creatorcontrib><creatorcontrib>Romano, Rosa</creatorcontrib><creatorcontrib>Garcia, Marta</creatorcontrib><creatorcontrib>Hervás-Salcedo, Rosario</creatorcontrib><creatorcontrib>Ugalde, Laura</creatorcontrib><creatorcontrib>Duarte, Blanca</creatorcontrib><creatorcontrib>Porteus, Matthew H.</creatorcontrib><creatorcontrib>Del Rio, Marcela</creatorcontrib><creatorcontrib>Larcher, Fernando</creatorcontrib><creatorcontrib>Murillas, Rodolfo</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bonafont, Jose</au><au>Mencía, Angeles</au><au>Chacón-Solano, Esteban</au><au>Srifa, Wai</au><au>Vaidyanathan, Sriram</au><au>Romano, Rosa</au><au>Garcia, Marta</au><au>Hervás-Salcedo, Rosario</au><au>Ugalde, Laura</au><au>Duarte, Blanca</au><au>Porteus, Matthew H.</au><au>Del Rio, Marcela</au><au>Larcher, Fernando</au><au>Murillas, Rodolfo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Correction of recessive dystrophic epidermolysis bullosa by homology-directed repair-mediated genome editing</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2021-06-02</date><risdate>2021</risdate><volume>29</volume><issue>6</issue><spage>2008</spage><epage>2018</epage><pages>2008-2018</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>Genome-editing technologies that enable the introduction of precise changes in DNA sequences have the potential to lead to a new class of treatments for genetic diseases. Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by extreme skin fragility. The recessive dystrophic subtype of EB (RDEB), which has one of the most severe phenotypes, is caused by mutations in COL7A1. In this study, we report a gene-editing approach for ex vivo homology-directed repair (HDR)-based gene correction that uses the CRISPR-Cas9 system delivered as a ribonucleoprotein (RNP) complex in combination with donor DNA templates delivered by adeno-associated viral vectors (AAVs). We demonstrate sufficient mutation correction frequencies to achieve therapeutic benefit in primary RDEB keratinocytes containing different COL7A1 mutations as well as efficient HDR-mediated COL7A1 modification in healthy cord blood-derived CD34+ cells and mesenchymal stem cells (MSCs). These results are a proof of concept for HDR-mediated gene correction in different cell types with therapeutic potential for RDEB.
[Display omitted]
By using CRISPR-Cas9 delivered as a ribonucleoprotein complex in combination with donor DNA templates delivered by adeno-associated viral vectors, Bonafont and colleagues describe highly efficient HDR-mediated gene correction in recessive dystrophic epidermolysis bullosa patient cells. This advanced therapy method opens the way to genome-editing treatments for genetic skin disease.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33609734</pmid><doi>10.1016/j.ymthe.2021.02.019</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6771-3561</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1525-0016 |
| ispartof | Molecular therapy, 2021-06, Vol.29 (6), p.2008-2018 |
| issn | 1525-0016 1525-0024 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8178438 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | AAV Cell Line Collagen Type VII - genetics CRISPR CRISPR-Cas Systems Dependovirus - genetics epidermolysis Epidermolysis Bullosa Dystrophica - genetics Epidermolysis Bullosa Dystrophica - therapy Gene Editing - methods Gene Expression gene therapy Gene Transfer Techniques Genes, Recessive Genetic Therapy - methods Genetic Vectors - genetics genome editing HDR Humans Keratinocytes - metabolism Mutation Original RDEB Recombinational DNA Repair skin |
| title | Correction of recessive dystrophic epidermolysis bullosa by homology-directed repair-mediated genome editing |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T21%3A36%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Correction%20of%20recessive%20dystrophic%20epidermolysis%20bullosa%20by%20homology-directed%20repair-mediated%20genome%20editing&rft.jtitle=Molecular%20therapy&rft.au=Bonafont,%20Jose&rft.date=2021-06-02&rft.volume=29&rft.issue=6&rft.spage=2008&rft.epage=2018&rft.pages=2008-2018&rft.issn=1525-0016&rft.eissn=1525-0024&rft_id=info:doi/10.1016/j.ymthe.2021.02.019&rft_dat=%3Cproquest_pubme%3E2491950673%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2491950673&rft_id=info:pmid/33609734&rft_els_id=S1525001621000861&rfr_iscdi=true |