Gene delivery with novel poly(l-tartaramidoamine)s

Gene delivery with polymeric vectors has recently developed as a practical alternative to viral delivery systems. In an effort to create nontoxic and highly effective synthetic transfection reagents, we have polymerized a tartarate comonomer with a series of amine comonomers to yield a new family of copolymers for this purpose. Four new poly(Ltartaramidoamine)s (T1-T4) have been designed and studied. Results of gel shift assays indicate that the polymers can bind plasmid DNA (pDNA) at polymer nitrogen to pDNA phosphate (N/P) ratios higher than one. Dynamic light scattering experiments reveal that each polymer compacts pDNA into nanoparticles (polyplexes) in the approximate size range to be endocytosed by cultured cells. The polyplexes formed with T1-T4 and pDNA, containing the firefly luciferase reporter gene, were also examined for their gene expression and toxicity profiles with BHK-21 cells. The poly(L-tartaramidoamine)s exhibit high delivery efficiency without cytotoxic effects, indicating that these polymers show great promise as new gene delivery vehicles.