Navigating the next frontier in biomedicine: breakthroughs and insights in nucleic acid therapeutics

Nucleic acid therapeutics are rapidly emerging as a transformative drug paradigm, offering precise and programmable regulation of gene expression across a broad spectrum of diseases. This review summarizes recent advances in key platforms-including antisense oligonucleotides, siRNA, miRNA, mRNA, and aptamers-emphasizing their unique mechanisms of action and therapeutic potential. We systematically outline critical contributions of chemical modification and delivery engineering, including backbone and sugar modifications, site-specific design, N-acetylgalactosamine (GalNAc) conjugation, and lipid nanoparticles, which collectively enhance stability, target specificity, and clinical applicability. Finally, we discuss persistent challenges such as immune activation, large-scale manufacturing, and long-term safety, and provide perspectives on future directions involving CRISPR-based gene editing, synthetic biology, nanotechnology, smart delivery systems, and combination therapies, aiming to offer strategic insights for the development and clinical translation of nucleic acid drugs.