siRNA: Caveat Emptor for Preclinical Studies?

Small interfering RNA molecules (siRNA) are generating a lot of excitement in biomedical research for their ability to "knock down" specific genes– say, those of an invading virus or a tumor cell.

But because viruses tend to produce small pieces of RNA, the body often "interprets" siRNA as a viral infection and launches an immune response.  In the Februrary 2008 issue of Human Gene Therapy, Adam Judge and Ian Maclachlan of Protiva Biotherapeutics describe some of the consequences of this.  A major one is that studies testing siRNA in animals or humans might be prone to false positives, especially for medical conditions where the immune system is implicated in disease control.  The problem is (according to these authors, at least), there seems to be little consensus about how to design experimental controls to sift true from spurious claims of specific efficacy.  Yet another complication in the interpretation of preclinical studies, as well as the decision to initiate human testing.