The application of RNAi-based treatments for inflammatory bowel disease.

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic, relapsing, idiopathic inflammation of the gastrointestinal tract with no permanent cure. Present immunosuppressive and anti-inflammatory therapies are often ineffective and associated with severe side effects. An RNA interference (RNAi)-based approach in which small interfering RNA (siRNA) mediates specific downregulation of key molecular targets of the IBD inflammatory process may offer a precise, potent and safer alternative to conventional treatments. This review describes the aetiology of Crohn's disease and ulcerative colitis and the cellular and molecular basis for current treatments to highlight target candidates for an RNAi-based approach. Promising preclinical studies support an RNAi application; however, optimal siRNA designs that maximise potency and development of enabling technologies for site- and cellular-specific delivery are prerequisites for clinical translation.