Development of RNAi technology for targeted therapy — A track of siRNA based agents to RNAi therapeutics

RNA interference (RNAi) was intensively studied in the past decades due to its potential in therapy of diseases. The target specificity and universal treatment spectrum endowed siRNA advantages over traditional small molecules and protein drugs. However, barriers exist in the blood circulation system and the diseased tissues blocked the actualization of RNAi effect, which raised function versatility requirements to siRNA therapeutic agents. Appropriate functionalization of siRNAs is necessary to break through these barriers and target diseased tissues in local or systemic targeted application. In this review, we summarized that barriers exist in the delivery process and popular functionalized technologies for siRNA such as chemical modification and physical encapsulation. Preclinical targeted siRNA delivery and the current status of siRNA based RNAi therapeutic agents in clinical trial were reviewed and finally the future of siRNA delivery was proposed. The valuable experience from the siRNA agent delivery study and the RNAi therapeutic agents in clinical trial paved ways for practical RNAi therapeutics to emerge early.

Graphical abstractThe transformation of siRNA based agents into RNAi therapeutics is a process of overcoming barriers. siRNA agents functionalized with different technologies to achieve targeted therapy through local or systemic administration.Figure optionsDownload full-size imageDownload high-quality image (113 K)Download as PowerPoint slide