UMMS Affiliation

Department of Neurology

Publication Date

2019-12-13

Document Type

Article

Disciplines

Genetics and Genomics | Molecular, Cellular, and Tissue Engineering | Nervous System | Therapeutics | Viruses

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.

Keywords

AAV capsid library, AAV vector, adeno-associated virus vector, central nervous system, gene delivery, gene therapy, transduction efficiency

Rights and Permissions

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/).

DOI of Published Version

10.1016/j.omtm.2019.10.007

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

Journal/Book/Conference Title

Molecular therapy. Methods and clinical development

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

31788496

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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