Design of Polyphosphoester-DNA Nanoparticles for Non-Viral Gene Delivery

Development of safe and effective non-viral gene carriers is still critical to the ultimate success of gene therapy. This review highlights our attempt to design the gene carriers in a systematic manner. We have synthesized a series of polymers with a phosphoester backbone containing different charge groups in the sidechain connected to the backbone through a phosphate (PO) or a phosphoramide (PN) bond. These gene carriers have different charge groups, sidechain lengths, and branching structures, but they are structurally related to allow a systematic investigation of the structure-property relationship, including DNA binding capacity, cytotoxicity, DNA protection, biodegradability, DNA release kinetics, and transfection efficiency.