A single-cell map of antisense oligonucleotide activity in the brain.

ABSTRACT: Antisense oligonucleotides (ASOs) dosed into cerebrospinal fluid (CSF) distribute broadly throughout the brain and hold the promise of treating myriad brain diseases by modulating RNA. CNS tissue is not routinely biopsied in living individuals, leading to reliance on CSF biomarkers to inform on drug target engagement. Animal models can link CSF biomarkers to brain parenchyma, but our understanding of how individual cells contribute to bulk tissue signal is limited. Here we employed single nucleus transcriptomics on tissue from mice treated with RNase H1 ASOs against Prnp and Malat1 and macaques treated with an ASO against PRNP . Activity was observed in every cell type, though sometimes with substantial differences in magnitude. Single cell RNA count distributions impl

SUBMITTER: Mortberg MA 

PROVIDER: S-EPMC9948956 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature