Year: 2026
Type: article
Abstract: Nucleic acid therapeutics (NATs) are a maturing drug class with many active clinical trials and a growing number of approvals. For NATs such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), a major hurdle during the research and development phase lies in selecting preclinical model systems with meaningful readouts on molecular and phenotypic efficacy. Key questions include: Which in vitro models are best positioned to quantify NAT activity and identify hits? In advancing a NAT from in vitro to in vivo studies, when is it appropriate to employ a surrogate or humanize a target locus; conversely, when is it appropriate to rely solely on human-derived cells? In this review, we will introduce and critique current approaches to ASO and siRNA preclinical efficacy studies and consider future advances in this fast-moving therapeutic area.
Source: Communications Biology
Authors: Peter L. Oliver, Alyssa C. Hill
Institutions: Research Complex at Harwell, University of Oxford
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funder: Medical Research Council
OpenAlex ID: W7128438807