Pentalysine-grafted ROMP polymers for DNA complexation and delivery

Amphiphilic graft polymers, containing oligolysine groups pendent to a hydrophobic polycyclooctene backbone, were used to form polyplexes with plasmid DNA pZsGreen1-N1. These poly(cyclooctene- graft-pentalysine) structures were found to be effective transfection reagents for COS-1 and HeLa cells. In the case of polymer 1e (average degree of polymerization of 206), protein expression levels 48 h post-transfection were found to be comparable to, or better than, commercial transfection reagents jetPEI and SuperFect. With HeLa cells, GFP expression levels were better than Lipofectamine 2000. Of particular interest was the excellent cell viability seen in experiments with polyplexes formed from the pentalysine-grafted polymers. In the example of the highest molecular weight graft copolymer, polymer 1e, cell viability relative to untreated cells was 99% with COS-1 cells and 92% with HeLa cells in contrast to the commercial reagents, which gave 67-80% with COS-1 cells and 17-52% with HeLa cells. The effectiveness of these polyolefin- graft-pentalysine structures as DNA delivery vehicles is attributed to their amphiphilic nature and branched architecture.