Therapeutic siRNAs

Interesting article on Biomed Central. siRNA are getting big in the research world; they allow to easily (and most of the time, specifically) knockdown expression of a gene by 50-95%. They are extremely usefull to study protein functions, but they also show lots of promise in therapeutic applications.

Imagine being able to knockdown expression of a viral or bacterial gene long enough for the immune system to get rid of it. Or knockdown expression of a gene linked to drug resistance in cancer cells. Until now, a (potential) problem undermined research in this area. siRNA are double-stranded RNA molecules; receptors (Toll-like receptors) on some cells recognize dsRNA as foreign (double-stranded RNA aren`t expected outside cells) and trigger an interferon-mediated immune response. Scientists feared that siRNA would trigger this response; when injected on a large scale in a living being, the intensity of it would be too strong and cause damage (or death). Scientists being what they are (curious), they had to try. They injected siRNAs designed against Luciferase (a firefly protein hydrolyzing luciferine, producing light) along with the plasmid encoding it (with appropriate negative and positive controls). Then they mesured IFN-gamma levels (elevated in case of a TLR-mediated immune response). Not only did the siRNA reduce levels of luciferase appreciably, but a total absence of IFN-gamma response was observed. It seem that the length (20-22 bases) of siRNA could explain the phenomenon. I don't need to tell you that these are excellent news for future siRNA-mediated therapy. Read the paper on Nature Biotech.