From RNA design to delivery: Computational strategies for functional RNA therapeutics

RNA therapeutics provide a revolutionary means of treating a variety of diseases by precisely regulating gene expression and protein synthesis, with great medical significance. However, there are three key challenges to its clinical application: the inherent instability of RNA, the need for controlled regulation of RNA function, and the lack of an efficient delivery system. Computational strategies provide complementary tools for analyzing and optimizing RNA sequence, structure, function, and delivery, accelerating the rational design of RNAs and the optimization of delivery systems. This review systematically introduces two core advances in the field of RNA therapy: (1) the design and optimization of RNAs based on predictive modeling and algorithmic screening; (2) the intelligent transformation of the delivery system through data-driven methods. Based on these developments, we discuss three future directions for computational RNA molecular design across the dimensions of design algorithms, design mechanisms, and design architectures. This review not only summarizes computational approaches developed to address key challenges in RNA therapeutics, but also highlights opportunities for integrated RNA-delivery co-design. These advances may provide useful insights for the development of next-generation precision therapeutics and their future clinical translation.