A disease-causing gene was silenced in monkeys through RNA interference (RNAi) therapy delivered into the bloodstream, scientists reported online yesterday (March 26) in Nature. This is the first study to show that systemic administration of RNAi works in non-human primates, and the findings affirm the promise of this new type of therapy, scientists say.
In the study, gene silencing using the highest dose persisted for 11 days, without any observed toxicity, a finding that “bodes well for future human systemic trials of RNAi therapies,” John Rossi of the Beckman Research Institute.
Scientists at Alnylam Pharmaceuticals and Protiva Biotherapeutics gave cynomolgus monkeys a single injection of small interfering RNAs (siRNAs) against the gene for apolipoprotein B (ApoB). This gene is involved in the assembly and secretion of low-density lipoprotein (LDL), and has not proven accessible to targeting with conventional small molecule or protein therapies.
Gene silencing occurred in a dose-dependent manner. Within 48 hours, the maximum level of APOB silencing exceeded 90%, with a more than 75% reduction in plasma ApoB and a more than 80% drop in LDL.