title: Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease.
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.
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Hadaczek
authors.affiliation: Rare Disease Unit, Neuroscience, Sanofi-Genzyme , Framingham, MA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Stanek
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Ciesielska
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Sudhakar
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: Lluis
authors.initials: L
authors.lastname: Samaranch
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Pivirotto
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: John
authors.initials: J
authors.lastname: Bringas
authors.affiliation: Rare Disease Unit, Neuroscience, Sanofi-Genzyme , Framingham, MA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: O'Riordan
authors.affiliation: Rare Disease Unit, Neuroscience, Sanofi-Genzyme , Framingham, MA, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Mastis
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: Waldy
authors.initials: W
authors.lastname: San Sebastian
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: John
authors.initials: J
authors.lastname: Forsayeth
authors.affiliation: Rare Disease Unit, Neuroscience, Sanofi-Genzyme , Framingham, MA, USA.
authors.forename: Seng H
authors.initials: SH
authors.lastname: Cheng
authors.affiliation: Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA.
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
authors.affiliation: Rare Disease Unit, Neuroscience, Sanofi-Genzyme , Framingham, MA, USA.
authors.forename: Lamya S
authors.initials: LS
authors.lastname: Shihabuddin