Model selection in preclinical nucleic acid therapeutics research
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.
Fields of Study & Subjects
RNA Interference and Gene Delivery
DNA and Nucleic Acid Chemistry
Advanced biosensing and bioanalysis techniques
Publication details
- Journal / source
- Communications Biology
- Publisher
- Springer Science and Business Media LLC
- Volume
- 9
- Issue
- 1
- Pages
- 200–200
- Publication date
- 9 February 2026
- Language
- EN