Journal
BIOMATERIALS SCIENCE
Volume 1, Issue 7, Pages 719-727Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3bm00006k
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Funding
- NIH [1DP2OD007246, 1R21EB013379]
- NSF [CHE 1153122]
- National Science Foundation (NSF) [0965918 IGERT]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1153122] Funding Source: National Science Foundation
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Diblock copolymers consisting of poly(ethylene glycol)-block-poly(gamma-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-bPVBLG- 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.
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