Stability modification of therapeutic aptamers: from biostability bottlenecks to nuclease-resistant construct design
Abstract
enzyme-resistant modifications has emerged as a cornerstone strategy in aptamer drug development. In this review, we systematically categorize current stabilization approaches across two complementary design dimensions: local-level modifications (including terminal modification, sugar modification, backbone modification, and base modification) and global structural-level engineering (including Spiegelmers, cyclization modification, and multivalent assembly). Furthermore, we discuss persistent translational challenges to illuminate a coherent framework for designing aptamers with high biostability that achieve enhanced nuclease resistance while concurrently exhibiting favorable pharmacokinetics, high target binding affinity and specificity.
Fields of Study & Subjects
Advanced biosensing and bioanalysis techniques
DNA and Nucleic Acid Chemistry
RNA Interference and Gene Delivery
Publication details
- Journal / source
- RSC Chemical Biology
- Publisher
- Royal Society of Chemistry (RSC)
- Volume
- 7
- Issue
- 6
- Pages
- 964–982
- Publication date
- 1 January 2026
- Language
- EN