209. Gene Silencing of Human Huntingtin Using Lentivirus-Delivered shRNA

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by polyglutamine expansion in huntingtin protein. Accumulation of mutant, toxic huntingtin in human patients and some HD mouse models leads to neurodegeneration, neurological impairment, and premature death. An effective treatment will require a reduction of mutant huntingtin. Induction of RNA interference (RNAi) by small hairpin RNA (shRNA) may be a feasible approach to suppress huntingtin gene expression and prevent its toxic accumulation in neurons. We hypothesize that stable expression of huntingtin-specific shRNA using feline immunodeficiency virus (FIV) vectors will provide long-term gene silencing, reduce mutant huntingtin expression and prevent or reverse HD-associated symptoms.