Light-Responsive Helical Polypeptides Capable of Reducing Toxicity and Unpacking DNA: Toward Nonviral Gene Delivery

摘要

Nonviral gene delivery with synthetic cationic polymeric vectors is widely recognized as an attractive alternative to viral gene delivery, which suffers from inherent immunoge-nicity and various side effects. The transfection efficiency and chemotoxicity of these polymeric vectors are often closely related to the density of their cationic charge. Materials with low charge density usually show low toxicity but are often poor transfection agents. Polycations with high charge density could mediate effective gene transfer, which is however often associated with significant, charge-induced toxicity. When modified with various charge-reducing moieties, including saccharides, hydrocarbons,' and polyethylene glycol) (PEG), polycations often benefit from improved safety profiles while in the meantime suffer from significantly reduced gene delivery capabilities. In addition to the charge-induced toxicity, excessive positive charges on polycations would also enhance the electrostatic attraction with the nucleic acids to restrict intracellular gene release. Therefore, it would be of great interest to develop a highly charged polycation that possesses full transfection capacity and membrane activity during gene transfer, but can be triggered to transform to a less charged or uncharged material with low membrane activity after transfection, such that intracellular DNA unpacking can be facilitated and toxicity can be reduced.