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 (M(W) = 2800, M(n) = 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 M(W) 2000 or 25,000. This polycationic gene carrier was synthesized by reacting low molecular weight PEI (M(W) = 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.
Xu
Songlin
S
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Chen
Moying
M
Yao
Yi
Y
Zhang
Zhiqun
Z
Jin
Tuo
T
Huang
Ying
Y
Zhu
Hua
H
D000818:Animals; D019556:COS Cells; D002219:Carbamates / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D007097:Imines / Q000737:chemistry*; D011095:Polyethylenes / Q000737:chemistry*; D014162:Transfection
D002219:Carbamates; D004337:Drug Carriers; D007097:Imines; D011095:Polyethylenes; C505405:poly(ethylene imine); D049452:Green Fluorescent Proteins; D004247:DNA