Department of Neurology
Genetics and Genomics | Molecular, Cellular, and Tissue Engineering | Nervous System | Therapeutics | Viruses
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.
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
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
Molecular therapy. Methods and clinical development
Hanlon KS, Sena-Esteves M, Hudry E, Maguire CA. (2019). Selection of an Efficient AAV Vector for Robust CNS Transgene Expression. Open Access Articles. https://doi.org/10.1016/j.omtm.2019.10.007. Retrieved from https://escholarship.umassmed.edu/oapubs/4101
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.