The development and improvement of ribonucleic acid therapy strategies.

The biological understanding of RNA has evolved since the discovery of catalytic RNAs in the early 1980s and the establishment of RNA interference (RNAi) in the 1990s. RNA is no longer seen as the simple mid-product between transcription and translation but as potential molecules to be developed as RNA therapeutic drugs. RNA-based therapeutic drugs have gained recognition because of their ability to regulate gene expression and perform cellular functions. Various nucleobase, backbone, and sugar-modified oligonucleotides have been synthesized, as natural oligonucleotides have some limitations such as poor low nuclease resistance, binding affinity, poor cellular uptake, and toxicity, which affect their use as RNA therapeutic drugs. In this review, we briefly discuss different RNA therapeutic drugs and their internal connections, including antisense oligonucleotides, small interfering RNAs (siRNAs) and microRNAs (miRNAs), aptamers, small activating RNAs (saRNAs), and RNA vaccines. We also discuss the important roles of RNA vaccines and their use in the fight against COVID-19. In addition, various chemical modifications and delivery systems used to improve the performance of RNA therapeutic drugs and overcome their limitations are discussed.