Making RNAi work in therapeutic application is tricky, and here, Derek Lowe reports on a paper published in Nature last week that does a good job demonstrating just how much researchers don't know. They used RNAi to knock down VEGF, whose overactivation leads to macular degeneration. In the end, they found that many different small interfering RNA sequences can work, and what's really being targeted is TLR3, the cell surface receptor that works downstream on factors that turn off angiogenesis. "The companies that are already dosing RNAi therapies for macular degeneration have just discovered that there's an awful lot that they don't know about what they're doing, for one thing," Lowe writes. "On the flip side, there are a lot of human cell types with TLR3 receptors on them, and a lot of angiogenic disorders that could potentially be treated, at least partially, by targeting them in this manner."
Is There a Word for 'Promiscuous Binding' for RNAi?
Mar 31, 2008