widespread aav1- and aav2-mediated transgene expression in the nonhuman primate brain: implications for huntington's disease

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ID: 187932
2016
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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.
Reference Key
hadaczek2016molecularwidespread Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Piotr Hadaczek;Lisa Stanek;Agnieszka Ciesielska;Vivek Sudhakar;Lluis Samaranch;Philip Pivirotto;John Bringas;Catherine O'Riordan;Bryan Mastis;Waldy San Sebastian;John Forsayeth;Seng H Cheng;Krystof S Bankiewicz;Lamya S Shihabuddin
Journal international journal of zoology
Year 2016
DOI
10.1038/mtm.2016.37
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