Dual-Action Protein-siRNA Conjugates for Targeted Disruption of CD47-Signal Regulatory Protein α Axis in Cancer Therapy.

A series of successes in RNA interference (RNAi) therapies for liver diseases using lipid nanoparticles and -acetylgalactosamine have heralded a current era of RNA therapeutics. However, alternative delivery strategies are required to take RNAi out of the comfort zone of hepatocytes. Here we report SIRPα IgV/anti-CD47 siRNA (vS-siCD47) conjugates that selectively and persistently disrupt the antiphagocytic CD47/SIRPα axis in solid tumors.