Journey of siRNA: Clinical Developments and Targeted Delivery

Abstract

Since the evolutionary discovery of RNA interference and its utilization for gene knockdown in mammalian cell, a remarkable progress has been achieved in small interfering RNA (siRNA) therapeutics. siRNA is a promising tool, utilized as therapeutic agent against various diseases. Despite its significant potential benefits, safe, efficient, and target oriented delivery of siRNA is one of the major challenges in siRNA therapeutics. This review covers major achievements in clinical trials and targeted delivery of siRNAs using various targeting ligand-receptor pair. Local and systemically administered siRNA drug candidates at various phases in clinical trials are described in this review. This review also provides a deep insight in development of targeted delivery of siRNA. Various targeting ligand-siRNA pair with complexation and conjugation approaches are discussed in this review. This will help to achieve further optimization and development in targeted delivery of siRNAs to achieve higher gene silencing efficiency with lowest siRNA dose availability.

Keywords: GalNAc; RNA interference; clinical trial; gene silencing; siRNA; targeted delivery.