Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 2, Issue 3, Pages 326-335Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.5b00393
Keywords
human embryonic stem cells; nonviral gene delivery; polypeptides; human pluripotent stem cells; hyaluronic acid; CD44
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Funding
- NIH [1DP2OD007246, 1R21EB013379]
- UIUC from National Science Foundation (NSF) [0965918]
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Gene delivery is an important tool to study and manipulate human pluripotent stem cells for regenerative medicine purposes. Yet current methods of transient gene delivery to stem cells are still inefficient. Through the combination of biologically based concepts and material design, we aim to develop new methods to enhance the efficiency of gene delivery to stem cells. Specifically, we use poly(gamma-4-(((2-(piperidin-1-yl)ethypamino)methyl)benzyl-L-glutamate) (PVBLG-8), a membrane-active helical, cationic polypeptide, to condense plasmid DNA to form stable nanocomplexes, which are further coated with hyaluronic acid (HA). HA not only shields the positive charges of PVBLG-8 to reduce toxicity, but also acts as a targeting moiety for cell surface receptor CD44, which binds HA and facilitates the internalization of the nanocomplexes. Upon entering cells, HA is degraded by hyaluronidase in endosomes and PVBLG-8 is exposed, facilitating the endosomal escape of DNA/polypeptide complex. Our studies show that the coating of HA significantly increases gene transfection efficiency of DNA/PVBLG-8 nanocomplexes from about 28 to 36% with largely reduced toxicity.
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