The consideration of synthetic short interfering RNA for therapeutic use

Small RNA molecules can act as regulators of post-transcriptional gene silencing and can target any given protein via the RNA interference pathway. This leads to the high expectation of small interference RNA (siRNA) as a therapeutic platform. Many companies and organisations are active in this development, which consequently forces siRNA's pharmacokinetic studies because pharmacokinetics plays an important role in elucidating the pharmacodynamic and toxicological mechanism of test articles. In particular, pharmacokinetics is mandatory in investigational new drug application in many countries. Some pre-clinical and clinical pharmacokinetic results have already been published and the fate of siRNA compounds in biological matrices has been explored in depth. The elucidation of the siRNA's metabolism improves the rational design of siRNA for disease control. This review focuses on the study of synthetic siRNA pharmacokinetics, the challenges of siRNA as a therapeutic agent and the strategies involved for improving siRNA bioavailability from the view of siRNA metabolism.