Exploding Microbubbles, RNAi, and RXi
Jun04

Exploding Microbubbles, RNAi, and RXi

The Haystack saw a press release yesterday out of Worcester, Mass.-based RNAi therapeutic firm RXi Pharmaceuticals that was intriguing. The company has signed a pact with Royal Philips Electronics to explore “image-guided therapy concepts based on RNAi.” What the heck does that mean? We were curious so we reached out to RXi for a primer, which turned into a bit of an update on where the company has come in the last year. Before we get into translating the mouthful of techno-speak from Philips and RXi, a few words to explain RXi’s delivery approach. Most folks in the RNAi therapeutics world are focused on encapsulating the siRNA in a lipid nanoparticle or polymer-based system: the formulation (in theory) guides the drug to its target cell and, once inside, releases its therapeutic payload. Check out our article on siRNA delivery for more details on the challenges and current limitations of that strategy. RXi is working on “self delivery” technology, which it bought from Boulder, Co.-based Advirna. As the company’s CSO (and Advirna co-founder) Anastasia Khvorova told me yesterday, the company is combining oligonucleotides, short single-stranded strings of nucleic acids, with small bits of double-stranded siRNA. RXi makes hydrophobic modifications to that hybrid molecule that stabilize the structure and allow it to be taken up by the cell of interest. They wind up with a large complex that has been tricked out to behave like a small molecule. So what does Philips bring to the table? RXi hopes to improve the potency of its self-delivery RNAi molecules using Philips’ formulation technology, which traps drugs inside “microbubbles” that are sensitive to ultrasound pulses. After a drug is dosed, it travels to the tissue of interest and an ultrasound pulse is applied, causing the bubbles to explode and the drug to be released. It all sounds rather futuristic, but RXi thinks it could significantly improve the potency of its molecules by one-to-two orders of magnitude. “Our RNAi molecules are very good at getting into cells once they’re kind of in the proximity, whereas their technology helps us get into the right organs,” RXi’s CEO Noah Beerman says. It’s cool stuff, but will it work? It remains to be seen, but it’s nice that some outside-the-box thinking is getting play in the RNAi arena. As mentioned, many companies continue to beat the lipid nanoparticle drum, but that technology has yet to work across a wide range of diseases. The need for chemistry and engineering to step in and come up with some innovative approaches to RNAi delivery is great. It’s worth noting that all this shiny new technology is a bit of a departure...

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