title: Cationic, helical polypeptide-based gene delivery for IMR-90 fibroblasts and human embryonic stem cells.
abstract: Diblock copolymers consisting of poly(ethylene glycol)-block-poly(γ-4-(((2-(piperidin-1-yl)ethyl)amino)methyl)benzyl-L-glutamate) (PEG-b-PVBLG-8) were synthesized and evaluated for their ability to mediate gene delivery in hard-to-transfect cells like IMR-90 human fetal lung fibroblasts and human embryonic stem cells (hESCs). The PEG-b-PVBLG-8 contained a membrane-disruptive, cationic, helical polypeptide block (PVBLG-8) for complexing with DNA and a hydrophilic PEG block to improve the biocompatibility of the gene delivery vehicle. The incorporation of PEG effectively reduced the toxicity of the helical PVBLG-8 block without dramatically compromising the polymer's ability to destabilize membranes or form complexes with DNA. PEG-b-PVBLG-8 copolymers with low (n = 76) and high (n = 287) degrees of polymerization (n) of the PVBLG-8 block were synthesized and evaluated for gene delivery. PEG-b-PVBLG-8 diblock polymers with a high degree of polymerization have a greater transfection efficiency and lower toxicity in IMR-90 cells than the commercial reagent Lipofectamine 2000. The usefulness of PEG-b-PVBLG-8 was further demonstrated via the successful transfection of hESCs without a measured loss in cell pluripotency markers.
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (USA).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yen
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Gabrielson
authors.forename: Lichen
authors.initials: L
authors.lastname: Yin
authors.forename: Linna
authors.initials: L
authors.lastname: Guan
authors.forename: Isthier
authors.initials: I
authors.lastname: Chaudhury
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng