Combinatorial modification of degradable polymers enables transfection of human cells comparable to adenovirus

End-modified poly(β-amino ester)s or easy-to-synthesize degradable polymers, that are able to deliver DNA to primary human umbilical vein endothelial cells (HUVEC) at levels comparable to adenovirus at a Multiplicity of Infection (MOI) between 100 and 500, are developed. These polymer modifications dramatically enhance DNA delivery to ovarian tumors, and the development of polymeric vectors with gene delivery efficacy comparable to adenovirus could set a new benchmark in non- viral transfection capability. Numerous polymeric materials have been used for gene delivery, while significant steps have been made in improving delivery, efficacy remains generally low, particularly for primary cells. Results showed that small modifications to the termini of a polymer can significantly increase its in vivo activity, and the specific end- modified polymers described here may have utility in the treatment of ovarian cancer.