A CAG repeat-targeting artificial miRNA lowers the mutant huntingtin level in the YAC128 model of Huntington's disease.

ABSTRACT: Among the many proposed therapeutic strategies for Huntington's disease (HD), allele-selective therapies are the most desirable but also the most challenging. RNA interference (RNAi) tools that target CAG repeats selectively reduce the mutant huntingtin level in cellular models of HD. The purpose of this study was to test the efficacy, selectivity, and safety of two vector-based RNAi triggers in an animal model of HD. CAG repeat-targeting short hairpin RNA (shRNA) and artificial miRNA (amiRNA) were delivered to the brains of YAC128 mice via intrastriatal injection of AAV5 vectors. Molecular tests demonstrated that both the shRNA and amiRNA reduced the mutant huntingtin level by 50% without influencing endogenous mouse huntingtin. In addition, a concentration-dependent reduction in HTT aggr

SUBMITTER: Kotowska-Zimmer A 

PROVIDER: S-EPMC9126840 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature