Nature Technology Feature on RNAi Therapeutics

Last year I linked to this animated tour through the process of RNA interference (RNAi). Andrew Fire and Craig Mello won the Noble Prize in Medicine in 2006 for their discovery of RNAi. RNAi is natural mechanism for silencing gene expression.

The latest issue of Nature has a "Technology Feature" on RNAi therapeutics entitled "Small RNAs: Delivering the future" by Nathan Blow. Here is a sample:

The remarkable ability of short sequences of synthetic RNA to interfere with messenger RNA and thereby silence the activity of specific genes has proved incredibly helpful to geneticists wrestling with genetic function. And the push to harness this RNA interference (RNAi) for therapeutic use is now beginning to make headway. In the six years since the first paper reporting RNAi gene silencing in mammals was published1, at least six therapeutic programmes based on the concept have moved into clinical trials.

....Getting a small RNA to interfere with the right messenger RNA in the correct tissue and cell type at a safe, therapeutic level by systemic administration requires an exquisite degree of control — creating the need for different delivery vehicles and potentially even specialized targeting strategies. Animal studies2 have shown that it is possible for siRNAs delivered systemically to silence target genes. "What we have learned over the past couple of years is that systemic delivery of RNAi can be achieved, and there are a variety of methods that can be used to achieve it," says Maraganore. But he is also quick to note that there is no simple solution.

....The rapid advancement of RNAi-based therapeutics is leading Polyplus-transfections to explore the manufacturing aspects of delivery vehicles. The company develops and markets DNA, RNA and protein transfection and delivery reagents for both in vitro and in vivo applications. And with RNAi therapeutics on the cusp of entering the clinic, the company sees the need to produce delivery vehicles in bulk under governmental quality specifications or 'current good manufacturing practices' (cGMP) standards. "If you want to be able to get these into the clinics, you have to have cGMP-qualified delivery systems," says Erbacher.

Cheers,
Colin