Strategies and mechanisms for endosomal escape of therapeutic nucleic acids

Despite impressive recent establishment of therapeutic nucleic acids as drugs and vaccines, their broader medical use is impaired by modest performance in intracellular delivery. Inefficient endosomal escape presents a major limitation responsible for inadequate cytosolic cargo release. Depending on the carrier, this endosomal barrier can strongly limit or even abolish nucleic acid delivery. Different recent endosomal escape strategies and their hypothesized mechanisms are reviewed.