¹CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA, USA

Correspondence: Professor J Lieberman, The CBR Institute for Biomedical Research, Warren Alpert Building, 200 Longwood Avenue, Boston, MA 02115, USA. E-mail: lieberman@cbr.med.harvard.edu

Received 28 July 2005; Revised 8 September 2005; Accepted 21 October 2005; Published online 5 January 2006.

Abstract

As soon as RNA interference (RNAi) was found to work in mammalian cells, research quickly focused on harnessing this powerful endogenous and specific mechanism of gene silencing for human therapy. RNAi uses small RNAs, less than 30 nucleotides in length, to suppress expression of genes with complementary sequences. Two strategies can introduce small RNAs into the cytoplasm of cells, where they are active – a drug approach where double-stranded RNAs are administered in complexes designed for intracellular delivery and a gene therapy approach to express precursor RNAs from viral vectors. Phase I clinical studies have already begun to test the therapeutic potential of small RNA drugs that silence disease-related genes by RNAi. This review will discuss progress in developing and testing small RNAi-based drugs and potential obstacles.