Clinical Review

Science, medicine, and the future

RNA interference

BMJ 2004; 328 doi: 10.1136/bmj.328.7450.1245 (Published 20 May 2004)
Cite this as: BMJ 2004;328:1245

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  1. Julian Downward, principal scientist (downward@cancer.org.uk)1
  1. 1 Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX

    Introduction

    Over the past decade “RNA interference” has emerged as a natural mechanism for silencing gene expression. This ancient cellular antiviral response can be harnessed to allow specific inhibition of the function of any chosen target genes, including those involved in causing diseases such as cancer, AIDS, and hepatitis. RNA interference is already proving to be an invaluable research tool, allowing much more rapid characterisation of the function of known genes. More importantly, the technology considerably bolsters functional genomics to aid in the identification of novel genes involved in disease processes. But can RNA interference be used as an effective therapeutic strategy? Many people in the biotechnology industry are betting that it can, but first considerable problems relating to delivery to target cells will have to be solved. This problem has proved the undoing of previous wonder technologies such as gene therapy and antisense. This review discusses the promises and pitfalls of RNA interference in research and treatment.

    This article is based on a review of the literature on RNA interference and post-transcriptional gene silencing appearing in the PubMed database, along with personal experience of working in this field for the past four years. It also draws on consensus views expressed at several international conferences on RNA interference in 2003.

    Current understanding of RNA interference

    The first hints of the existence of the gene silencing mechanism that is now called RNA interference emerged from work on the genetic modification of plants in the late 1980s. Attempts to deepen the violet hue of petunias by expressing higher levels of an enzyme involved in the synthesis of the pigment unexpectedly resulted in the appearance of many white flowers. The introduction of extra copies of the gene had somehow caused a decrease in its expression rather than the anticipated increase.1 2

    For some time this remained an unexplained …

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