pH-responsive shielding of non-viral gene vectors

PEG shielding of non-viral vectors reduces undesired interactions with the extracellular environment. Combination with cell-binding domains enables in vivo targeting via specific attachment to the target cells. Pegylation, however, also interferes with effective intracellular nucleic acid delivery. Consistently triggered removal of the PEG shield after reaching the target cell would make non-viral vectors more compatible with the intracellular delivery steps. Physiological triggers may include changes in pH, enzyme concentration or redox potential. This review focuses on pH-sensitive shielding strategies that exploit the endosomal acidification process after endocytosis for deshielding of the delivery system.