Review article: RNA interference--potential therapeutic applications for the gastroenterologist.

BACKGROUND

A new technique of gene regulation, termed RNA interference, has emerged recently. RNA interference utilizes short double-stranded RNA to inhibit selectively gene expression of complementary RNA nucleotide sequences after transcription, but prior to translation. Gastrointestinal and hepatic disorders may be particularly amenable to therapeutic RNA interference intervention because of the relative ease of delivery of drugs to the gastrointestinal tract and liver.

AIM

To examine the published literature for potential clinical uses of RNA interference in gastroenterology and speculate on future therapies for luminal disease.

METHODS

Reports were identified using PubMed and the search term 'RNA interference', focusing on therapeutic uses related to gastrointestinal and liver disease.

RESULTS

Cellular and animal models demonstrate the potential application of short-interfering RNA-based therapies for viral hepatitis and inflammatory bowel disease. With validation of specific targets and better in vivo delivery of short-interfering RNA, RNA interference may represent a new frontier for molecular-targeted therapy in gastroenterology and hepatology.

CONCLUSIONS

Short-interfering RNA provides a novel and specific means to inhibit gene expression. Translation to the clinical arena will require further definition of side-effects, off-target effects and delivery systems. Ultimately, mucosally applied or endoscopically delivered short-interfering RNA could be one of the earliest clinical uses of short-interfering RNA therapy.