Clinical experiences with systemically administered siRNA-based therapeutics in cancer

Several Phase I trials evaluating the use of siRNA for the treatment of solid cancers have now been completed.All trials to date have used nanoparticle-based delivery systems to transport therapeutic siRNA to tumours following systemic administration.Despite concerns about potential overwhelming immunostimulation following systemic siRNA administration in humans, the data reported to date for clinically evaluated siRNA therapeutics (both naked and chemically modified siRNA) have shown these therapeutics to be well tolerated, with only modest and treatable immunostimulatory reactions.Successful delivery of functional siRNA to human tumours has been demonstrated in multiple trials, providing proof-of-principle for RNAi- based therapeutics in humans.Results from these trials show that safe target gene inhibition can be achieved in patients, when systemically treated twice per week with either lipid- or polymer-based nanoparticle formulations containing siRNAs at doses in the 0.5–1.0 mg siRNA per kg range.