Cyclodextrin-Based Nanoparticles for Delivery of Antisense Oligonucleotides Targeting Huntingtin.

ABSTRACT: Huntington's disease (HD) is a progressive inherited neurodegenerative disease caused by a CAG repeat expansion in the huntingtin gene, which is translated into the pathologic mutant huntingtin (mHTT) protein. Despite the great potential of HTT lowering strategies and the numerous antisense oligonucleotides (ASOs) in pre- and clinical trials, sustained silencing of mHTT has not been achieved. As a strategy to improve ASO delivery, cyclodextrin-based nanoparticles (CDs) offer a promising approach. Here, three CDs with distinct chemical structures were designed and their efficacies were compared as potential platforms for the delivery of ASO targeting HTT. Results using striatal neurons and HD patient-derived fibroblasts indicate that modified γ-CDs exhibited the best uptake efficiency and s

SUBMITTER: Mendonca MCP 

PROVIDER: S-EPMC9965918 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature