Step 1: Drug delivery

Often the hardest part of getting a new drug working and on the market is the problem of delivery–how to get the drug itself to the correct place in the body. New research published in Nature usues nanoparticles as a way to deliver siRNA (small interfering RNA) directly to cells in the vaginal wall. The technology was developed with anti-HIV drugs in mind. The research done in mice shows succesful delivery of siRNA for green fluorescent protein (GFP) to these cells. Once the siRNA is active, GFP expression, readily visible under blue light, disappears from the “treated” cells. The idea is to use siRNA that targets HIV RNAs to similarly “turn-off” HIV.

RNA interfernce machinery is uibuquitous in eukaryotic cells [read: cells that people are made of] and is though to have developed as a way to protect the host genome [read: your DNA] from intruding viral RNAs. Using this to combat HIV is exciting. Since the siRNA disrupts the HIV pathway before the RNA can be reverse transcribed to DNA, I’m thinking this is a “reverse transcriptase inhibitor” type drug, but the news article doesn’t specify. Either way, the idea of embedding the drug in nanoparticles suggests a gel-type application system, putting it in the realm of microbicides, none of which have passed clinical trials yet.

The research team also realized the obstacles they still have to overcome– firstly, evidence that this system will be effective at knocking down HIV RNA. Trials in monkeys are apparently ongoing. Second, the amount of siRNA needs to be enough so that all cells containing HIV are targeted, otherwise, infection will still occur.

The importance of microbicides for women in sub-Saharan Africa is that it would give women a way to protect themselves without having to use a condom–an issue that can be stressful to women and cause suspicion from husbands. The most recent microbicide trial has been the most promising for reducing the chance of HIV infection, but still not statistically significant. However, another trial is scheduled for this same drug later this year.

For the siRNA paper see: Woodrow K.A. et al. Nature Mater. advanced online publication doi: 10.1038/NMAT2444 (2009).


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