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

Antisense oligonucleotides (ASOs) dosed into cerebrospinal fluid (CSF) distribute broadly throughout the central nervous system (CNS). By modulating RNA, they hold the promise of targeting root molecular causes of disease and hold potential to treat myriad CNS disorders. Realization of this potential requires that ASOs must be active in the disease-relevant cells, and ideally, that monitorable biomarkers also reflect ASO activity in these cells.

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

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.