Selection of an Efficient AAV Vector for Robust CNS Transgene Expression
Name:
Publisher version
UMass Chan Affiliations
Department of NeurologyDocument Type
Journal ArticlePublication Date
2019-12-13Keywords
AAV capsid libraryAAV vector
adeno-associated virus vector
central nervous system
gene delivery
gene therapy
transduction efficiency
Genetics and Genomics
Molecular, Cellular, and Tissue Engineering
Nervous SystemTherapeuticsViruses
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Show full item recordAbstract
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.Source
Mol Ther Methods Clin Dev. 2019 Oct 23;15:320-332. doi: 10.1016/j.omtm.2019.10.007. eCollection 2019 Dec 13. Link to article on publisher's site
DOI
10.1016/j.omtm.2019.10.007Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41316PubMed ID
31788496Notes
Full author list omitted for brevity. For the full list of authors, see article.
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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/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/Scopus Count
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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/).