Chemical Modification and Delivery System of Small Interfering RNA Drugs

In the past decade, nucleic acid therapeutics have experienced rapid development, with RNA interference (RNAi) based technology emerging as a versatile tool widely used in the treatment of various diseases. Small interfering RNA (siRNA), as a sequence-specific gene silencing method, has provided an effective and specific means for studying gene function and developing new therapeutic strategies. Consequently, there has been significant interest in utilizing siRNA as a method to target specific gene functions in therapy. However, in order to make RNAi technology valuable and effective, it is crucial to chemically modify siRNA and develop efficient siRNA delivery strategies. These measures aim to improve the stability and cellular uptake capability of siRNA, enhance sequence specificity, and reduce non-specific gene silencing and biotoxicity. This review provides a concise introduction to the chemical modifications of siRNA aimed at enhancing its resistance to nucleases and stability. Additionally, the development of siRNA delivery systems, including lipid-based and polymer-based carrier systems, represents a significant research direction. These systems aim to improve the pharmacokinetics of siRNA, enhance intracellular delivery, and achieve tumor targeting. Finally, this review summarizes and discusses the technological bottlenecks and future trends in siRNA drug delivery, providing guidance for the further application of siRNA as a therapeutic strategy.