Polyelectrolyte vectors for gene delivery: Influence of cationic polymer on biophysical properties of complexes formed with DNA

Cationic polymer/DNA complexes are widely used for gene delivery, although the influence of the cationic polymer on the biophysical properties of the resulting complex is poorly understood. Here, several series of cationic po lymers have been used to evaluate the influence of structural parameters on properties of DNA complexes. Parameters studied included the length of sid e chain, charge type (primary versus tertiary and quaternary), polymer mole cular weight, and charge spacing along the polymer backbone. Cationic polym ers with short side chains (such as polyvinylamine) formed small complexes, resistant to destabilization by polyanions, with low surface charge, limit ed transfection activity, and efficient intranuclear transcription. Convers ely, cationic polymers with long side chains (e.g., poly[methacryloyl-Gly-G ly-NH-(CH2)(6)-NH2)] showed inefficient complex formation, high positive su rface charge, and better transfection activity. The effects of molecular we ight varied between polymers, for example, low molecular weight poly(L-lysi ne) produced relatively small complexes, whereas low molecular weight poly[ 2-(trimethylammonio)ethyl methacrylate chloride] produced large aggregates. Polymers containing quaternary ammonium groups showed efficient complex fo rmation but poor transfection. Finally, spreading charges widely on the pol ymer structure inhibited their ability to condense DNA. In summary, to achi eve small, stable complexes, the use of cationic polymers with short side c hains bearing primary amino groups is suggested.