RNAi Therapeutic Potentials and Prospects in CNS Disease

Abstract

Over the past 20 years, RNA interference (RNAi) technology has provided a new regula‐ tory paradigm in biology. This technique can efficiently suppress target genes of interest in mammalian cells. Small non-coding RNAs play important roles in gene regulation, in‐ cluding both in post-transcriptional and in translational regulation. For in vivo experi‐ ments, continuous development has resulted in successful new ways of designing, identifying, and delivering small interfering RNAs (siRNAs). Proof-of-principle studies in vivo have clearly demonstrated that both viral and non-viral delivery methods can pro‐ vide selective and potent target gene suppression without any clear toxic effects. There are also the persistent problems with off-target effects (OTEs), competition with cellular RNAi components, and effective delivery in vivo. Although recent researches and trials from a large number of animal model studies have confirmed that most OTEs are not dangerous, other important issues need to be addressed before RNAi-based drugs are ready for clinical use. Currently, RNAi may be harnessed as a new therapeutic modality for brain diseases. Finally, there are already several RNAi-based human clinical trials in progress. It is hoped that this technology will have also effective applications in human central nervous system (CNS)-related disease.