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Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease.
- Source :
-
Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2016 Jun 29; Vol. 3, pp. 16037. Date of Electronic Publication: 2016 Jun 29 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- Huntington's disease (HD) is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt) protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV), AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP), with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.
Details
- Language :
- English
- ISSN :
- 2329-0501
- Volume :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular therapy. Methods & clinical development
- Publication Type :
- Academic Journal
- Accession number :
- 27408903
- Full Text :
- https://doi.org/10.1038/mtm.2016.37