Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides.

ABSTRACT: The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein leve

SUBMITTER: Bost JP 

PROVIDER: S-EPMC8888659 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature