A year ago Roche rocked the RNA interference (RNAi) sector by shutting down its operations and followed up last week by selling its delivery assets to Arrowhead Research. While some big pharma have gone cold on RNAi, others, like Arrowhead, still expect the sector to be a success.
“Aptamers can be a very effective vehicle for delivering siRNA”, John Rossi, professor at the Beckman Research Institute of City of Hope, said at an AAPS 2011 conference session.
By using an aptamer delivery vehicle Rossi has delivered siRNA to HIV-infected cells in mouse models. Treatment with the formulation caused a 1m-fold drop in viral load, Rossi said, and only targeted HIV-infected cells.
Rossi has also researched the use of dendrimers as a non-targeted delivery vehicle. Again, the technique has shown promise and Rossi thinks siRNA can at least be used as an adjuvant in the treatment of HIV.
Many promising preclinical candidates have failed in the clinic though and Rossi said the first to enter Phase I was “ill-fated”. Stabilisation, off-target effects, duration, toxicity via competition with endogenous miRNA and, in particular, delivery are problems for siRNA in clinical trials.
“In cell culture RNAi is a great tool but in animal models there are delivery challenges we need to address”, Majid Moridani, director, pharmacokinetics laboratory at National Jewish Health, said at AAPS.
Most RNAi treatments in clinical trials lack a dedicated delivery vehicle, Rossi said, but many administration tools are in development. Rossi said dendrimers and aptamers have potential but other speakers at AAPS highlighted alternative techniques.
Lisbeth Illum, CEO of Critical Pharmaceuticals, said nasal delivery has potential as a route of administration for siRNA and miRNA. At the same session Raphael Mannino, professor at the University of Medicine and Dentistry of New Jersey, said cochleates can deliver siRNA too.