Selection of an Efficient AAV Vector for Robust CNS Transgene Expression
| dc.contributor.author | Hanlon, Killian S. | |
| dc.contributor.author | Sena-Esteves, Miguel | |
| dc.contributor.author | Hudry, Eloise | |
| dc.contributor.author | Maguire, Casey A. | |
| dc.date | 2022-08-11T08:09:55.000 | |
| dc.date.accessioned | 2022-08-23T16:48:41Z | |
| dc.date.available | 2022-08-23T16:48:41Z | |
| dc.date.issued | 2019-12-13 | |
| dc.date.submitted | 2020-01-21 | |
| dc.identifier.citation | <p>Mol Ther Methods Clin Dev. 2019 Oct 23;15:320-332. doi: 10.1016/j.omtm.2019.10.007. eCollection 2019 Dec 13. <a href="https://doi.org/10.1016/j.omtm.2019.10.007">Link to article on publisher's site</a></p> | |
| dc.identifier.issn | 2329-0501 (Linking) | |
| dc.identifier.doi | 10.1016/j.omtm.2019.10.007 | |
| dc.identifier.pmid | 31788496 | |
| dc.identifier.uri | http://hdl.handle.net/20.500.14038/41316 | |
| dc.description | <p>Full author list omitted for brevity. For the full list of authors, see article.</p> | |
| dc.description.abstract | Adeno-associated virus (AAV) capsid libraries have generated improved transgene delivery vectors. We designed an AAV library construct, iTransduce, that combines a peptide library on the AAV9 capsid with a Cre cassette to enable sensitive detection of transgene expression. After only two selection rounds of the library delivered intravenously in transgenic mice carrying a Cre-inducible fluorescent protein, we flow sorted fluorescent cells from brain, and DNA sequencing revealed two dominant capsids. One of the capsids, termed AAV-F, mediated transgene expression in the brain cortex more than 65-fold (astrocytes) and 171-fold (neurons) higher than the parental AAV9. High transduction efficiency was sex-independent and sustained in two mouse strains (C57BL/6 and BALB/c), making it a highly useful capsid for CNS transduction of mice. Future work in large animal models will test the translation potential of AAV-F. | |
| dc.language.iso | en_US | |
| dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31788496&dopt=Abstract">Link to Article in PubMed</a></p> | |
| dc.rights | Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | AAV capsid library | |
| dc.subject | AAV vector | |
| dc.subject | adeno-associated virus vector | |
| dc.subject | central nervous system | |
| dc.subject | gene delivery | |
| dc.subject | gene therapy | |
| dc.subject | transduction efficiency | |
| dc.subject | Genetics and Genomics | |
| dc.subject | Molecular, Cellular, and Tissue Engineering | |
| dc.subject | Nervous System | |
| dc.subject | Therapeutics | |
| dc.subject | Viruses | |
| dc.title | Selection of an Efficient AAV Vector for Robust CNS Transgene Expression | |
| dc.type | Journal Article | |
| dc.source.journaltitle | Molecular therapy. Methods and clinical development | |
| dc.source.volume | 15 | |
| dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5120&context=oapubs&unstamped=1 | |
| dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/oapubs/4101 | |
| dc.identifier.contextkey | 16292491 | |
| refterms.dateFOA | 2022-08-23T16:48:41Z | |
| html.description.abstract | <p>Adeno-associated virus (AAV) capsid libraries have generated improved transgene delivery vectors. We designed an AAV library construct, iTransduce, that combines a peptide library on the AAV9 capsid with a Cre cassette to enable sensitive detection of transgene expression. After only two selection rounds of the library delivered intravenously in transgenic mice carrying a Cre-inducible fluorescent protein, we flow sorted fluorescent cells from brain, and DNA sequencing revealed two dominant capsids. One of the capsids, termed AAV-F, mediated transgene expression in the brain cortex more than 65-fold (astrocytes) and 171-fold (neurons) higher than the parental AAV9. High transduction efficiency was sex-independent and sustained in two mouse strains (C57BL/6 and BALB/c), making it a highly useful capsid for CNS transduction of mice. Future work in large animal models will test the translation potential of AAV-F.</p> | |
| dc.identifier.submissionpath | oapubs/4101 | |
| dc.contributor.department | Department of Neurology | |
| dc.source.pages | 320-332 |
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Except where otherwise noted, this item's license is described as Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).