Format

Send to

Choose Destination
Mol Ther Methods Clin Dev. 2016 Jun 29;3:16037. doi: 10.1038/mtm.2016.37. eCollection 2016.

Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease.

Author information

1
Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
2
Rare Disease Unit, Neuroscience, Sanofi-Genzyme , Framingham, MA, USA.

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.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center