Clostridial translocation peptides for promoting endosomal escape of RNAi agents (WO09083738)

Abstract

Pharmacological agents harnessing the potency of RNAi (RNA interference) are currently receiving the lion's share of the attention within the drug delivery field, but their clinical utility is unfortunately hampered by their inherent physico-chemical characteristics and pharmacokinetic properties. The patent application WO09083738 pertains to RNA delivery vehicles comprising clostridial neurotoxin-derived polypeptides, for enhancing the intracellular availability of RNAi-inducing pharmacological agents, primarily siRNAs. The present patent evaluation assesses the utility of the claimed delivery vehicles, as well as the merits of the disclosure as a whole, in light of alternative siRNA delivery strategies. WO09083738 discloses the purported usefulness of clostridial translocation domains and non-cytotoxic proteases, as well as targeting moieties and numerous other constituents, for improving delivery of siRNA agents. Despite the potentially interesting delivery concept, and the numerous embodiments encompassed within the highly extensive application, the limited extent of the experimental data is surprising, in particular in view of the broad claims. Thus, considering the increasingly rigorous demands for experimental support placed on life science patent applications, additional in vitro and in vivo validation would undoubtedly have strengthened the case for WO09083738.