Development of gene-specific double-stranded RNA drugs

Abstract

A relatively recent entrant into molecular biology--double-stranded RNA (dsRNA)--as a class exhibits a unique set of properties: relative stability, affinity for specific proteins and enzymes, ability to activate the interferon pathway and finally, RNA interference (RNAi). In RNAi, unique double-stranded short interfering RNA molecules (siRNA) destroy the corresponding target RNA with exquisite potency and selectivity, thus causing post-transcriptional gene silencing (PTGS). An understanding of the design of gene-specific dsRNA and development of techniques to deliver dsRNA in the cell and in live animals has heralded a new age of gene therapy without gene knockout. This review first summarizes the biological synthesis, metabolism and effect of the dsRNA with special emphasis on siRNA and RNAi. This is followed by the clinical, pharmacological and pharmaceutical prospects of the development of the dsRNA as a drug. It is clear that the dsRNA holds an enormous promise in the treatment of a large number of metabolic and infectious diseases including but not limited to cancer, macular degeneration, diabetic retinopathy, Alzheimer's and other neural disorders, autoimmune diseases, and all viral infections including AIDS (acquired immune deficiency syndrome), hepatitis and respiratory syncytial virus (RSV).