Aptamer-RNA conjugates for precision medicine: Design principles, therapeutic applications, and future perspectives
Annual Reports in Medicinal Chemistry, Academic Press , 2026
- Yayın Türü: Kitapta Bölüm / Araştırma Kitabı
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/bs.armc.2026.08.002
- Yayınevi: Academic Press
- Anahtar Kelimeler: Aptamer, Aptamer-RNA conjugates, Precision medicine, SELEX, Targeted nucleic acid therapeutics, Targeted RNA delivery
- Hatay Mustafa Kemal Üniversitesi Adresli: Evet
Özet
Aptamer-RNA conjugates stand out as a promising class of targeted nucleic acid therapeutics, combining the high affinity and target-specific recognition capacity of aptamers with the gene-regulating activity of therapeutic RNAs. These hybrid constructs, integrating selective molecular recognition with RNA-mediated biological activity, offer an attractive strategy to overcome the major limitations of traditional RNA therapeutics, such as low stability, limited cellular uptake, rapid degradation, and off-target effects. This section comprehensively addresses the design principles, biochemical properties, and biomedical applications of aptamer-RNA conjugates. First, the molecular properties of aptamers, SELEX-based selection technologies, three-dimensional folding and target recognition mechanisms, and the advantages they offer compared to antibody-based recognition agents are introduced. Then, covalent single-strand chimeras, chemical linker-mediated coupling, hybridization-based coupling, and nanocarrier-assisted strategies are examined, along with the cleavable and non-cuttable linker chemistries that determine stability, pharmacokinetics, intracellular transport, and controlled payload release. This chapter reviews highlighting advances in the use of aptamer-siRNA, aptamer-miRNA/anti-miRNA, and aptamer-shRNA chimeras in cancer, viral infections, inflammatory diseases, and rare diseases. Finally, major barriers to clinical translation, including nuclease-induced degradation, inadequate endosomal escape, heterogeneous receptor expression, immunogenicity, toxicity, manufacturing complexity, and regulatory challenges, are critically evaluated. Emerging approaches such as advanced chemical modifications, multifunctional nanocarriers, AI-assisted aptamer design, and personalized targeting are also discussed, demonstrating the potential of these conjugates to be programmable, safe, and effective therapeutics for next- generation precision medicine.