Novel poly(ethylene imine) biscarbamate conjugate as an efficient and nontoxic gene delivery system

We report a novel poly(ethylene imine) biscarbamate conjugate (PEIC) with a low molecular weight (MW = 2800, Mn = 910), and low cytotoxicity which has orders of magnitude higher luciferase gene transfection activity at its optimal conditions as compared with poly(ethylene imines) (PEIs) of MW 2000 or 25,000. This polycationic gene carrier was synthesized by reacting low molecular weight PEI (MW = 800) with 1,4-Butanediol bis(chloroformate) to give a copolymer with biodegradable carbamate linkages. When added to a DNA solution, PEIC condensed DNA at a w/w ratio above 1 to form 53–91 nm polyplexes with 20–24 mV in zeta potential (about half of that of branched 25kDa PEI). PEIC can also transfect MeWo cells with large genes such as the 125kb Varicella–Zoster viral gene (VZV) at high activity.