Promising RNAi therapeutics research also is advancing in academic labs. In March of last year, John Rossi at the Beckman Research Institute of City of Hope published a paper in Science Translational Medicine showing that attaching an aptamer to a small piece of double-stranded RNA (known as a small interfering RNA or siRNA) could provide a dual way of attacking HIV. The aptamer itself showed the ability to neutralize free-floating HIV in infected mice, and when attached to the siRNA, it ferried the siRNA into HIV-infected cells. Results showed a significantly reduced viral load in the animals treated with the combination. Rossi says the team currently is experimenting with using different siRNAs to attack multiple HIV genes at once.
He adds that Dicerna Pharmaceuticals, the RNAi therapeutics company he co-founded in 2007 based on his findings that slightly longer siRNAs than those commonly used have a more potent knock-down effect, actually got a boost while other pharma companies were pulling back. Around the time Roche announced its own RNAi program termination, Japanese pharma company Kyowa Hakko Kirin forged a $1.4 billion agreement with Dicerna.
“We’re really doing well at this point,” says Rossi, who still serves as chair of the company’s scientific advisory board.
In March of last year, chemical engineer Mark Davis of the California Institute of Technology published the results of a small Phase 1 trial of an RNAi drug targeting solid tumors aided by a nanoparticle delivery system. These encapsulated siRNAs were the right size, about 70 nanometers, to escape the leaky blood vessels that surround tumors, and they were tagged with transferin, a protein for which many cancer cells carry receptors on their surfaces. This combo allowed the siRNAs to specifically bombard tumors.
The trial showed that the therapy was safe, and biopsies from some of the volunteers’ tumors showed the RNAi was doing its job – the targeted mRNA was cleaved at just the spot where the researchers would expect. Davis and his colleagues currently are testing the therapy in a larger trial, proof that they’re not giving up anytime soon on RNAi.
“Despite what pharma says about RNAi, I think it’s a really exciting area,” he says. “I like to tell my students to work on something of high significance. It will be hard, of course, but I’d rather go down in flames working on something with high significance than something people don’t really care about.”
Christen Brownlee (firstname.lastname@example.org) is a freelance science writer based in Baltimore, Md.