Aptamer-ODN Chimeras: Enabling Cell-Specific ODN Targeting Therapy.

Oligonucleotides (ODNs) such as siRNA, saRNA, and miRNA regulate gene expression through a variety of molecular mechanisms and show unique potential in the treatment of genetic diseases and rare diseases, but their clinical application is still limited by the efficiency of the delivery system, especially the problem of the insufficient targeting of extrahepatic tissues. As homologous nucleic acid molecules, aptamers have become a key tool to improve the targeted delivery of ODNs. Aptamer-ODN chimeras can not only bind to multiple proteins on the cell surface with high specificity and selectivity, but they can also internalize into cells. Furthermore, they outperform traditional delivery systems in terms of cost-effectiveness and chemical modification flexibility. This review systematically summarizes the origin and progress of aptamer-ODN chimera therapy, discusses some innovative design strategies, and proposes views on the future direction of aptamer-ODN chimeras.