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WVE > Xconomy article has some more info...

WaVe Gets $18M to Solve RNA’s “Underappreciated” Chemistry Problem

http://www.xconomy.com/boston/2015/02/02/wave-gets-18m-to-solve-rnas-underappreciated-chemistry-problem/

The new round is being led by RA Capital Management and Kagoshima Shinsangyo Sosei Investment; SNBL took part as well. RA Capital founding partner Peter Kolchinsky is joining WaVe’s board as part of the funding.

So why does WaVe think it can make better RNA drugs? It has to do with what’s known as chirality, chemistry’s version of handedness. Just as the right and left hand have all the same components, but arranged in mirror images of one another, many drug molecules have different versions that are composed of the same atoms but in mirrored arrangements—and it turns out that handedness sometimes has a dramatic effect on the body’s response to the molecule. Thalidomide’s notorious propensity for causing birth defects is due to one version of the molecule, for instance, while its desired sedative effects are produced by the mirrored version.

WaVe’s claim—something it’ll have to prove—is that chirality is important for RNA drugs too. Bolno says that this concept has largely been “ignored” when it comes to nucleic acids and antisense drugs, but that it shouldn’t be, because it limits their potential and potency. What’s more, these molecules are larger and more complex than traditional drugs—with more places along their length for atoms to be attached in a left- or right-handed configuration. Current techniques for synthesizing these molecules don’t control for that, so they produce a mixture of thousands of different versions of a would-be drug—each with “unique pharmacology,” Bolno says.

“That’s been underappreciated,” he says.

For his part, Bolno says this is because the issue was ”not possible to address” before WaVe came along. But the question is whether it matters. WaVe contends that it does, and that the company has developed a way to control the chirality of the RNAs it produces. WaVe is starting out using this to develop antisense compounds—Isis’s specialty—and Bolno contends that the process could be applicable to other RNA drug methods, like exon-skipping, RNA interference, and micro RNAs.