Design of Poly(vinyldiaminotriazine)‐Based Nonviral Vectors via Specific Hydrogen Bonding with Nucleic Acid Base Pairs

A novel gene transfer system that complexes plasmid DNA (pDNA) through complementary hydrogen bonding of guests with base pairs is reported. Poly(vinyldiaminotriazine) (PVDT) homopolymer and its copolymers with poly(1‐vinyl‐2‐pyrrolidone) are synthesized via conventional radical random polymerization, and water‐soluble fractions are collected. These PVDT‐based polymers efficiently complex pDNA and displace ethidium bromide (EB) in EB‐intercalated pDNA solutions because of the hydrogen‐bonding‐induced constrained state of pDNA. It is also found that upon complexation, pDNA seems to undergo B–C conformation change and circular dichroism spectra assumed a polymer‐and‐salt‐induced (psi)‐type pattern that is rationally ascribed to a certain change in the high‐order structure of DNA condensates. Transmission electron microscopy presented several morphologies of spheres and toroids within aggregates ≥ 100 nm, resembling DNA condensation induced by cationics. In transfection studies using pDNA‐encoding luciferase or enhanced green fluorescent protein, this system could efficiently transfect COS‐1 cells. Compared to the commercial polycation system, ExGen 500, these H‐bonding vectors display several merits such as higher transfection efficiency, lower cytotoxicity, better serum compatibility, and stability in the presence of bovine serum albumin (BSA). The results suggest that PVDT‐based polymers are superior to polycation counterparts with regard to their potential in vivo applications.