Effective Gene Delivery into Human Stem Cells with a Cell-Targeting Peptide-Modified Bioreducible Polymer

Title
Effective Gene Delivery into Human Stem Cells with a Cell-Targeting Peptide-Modified Bioreducible Polymer
Authors
신흥수
Keywords
STABLE TRANSGENE EXPRESSION; SIRNA DELIVERY; ACETYLCHOLINE-RECEPTOR; POLY(DISULFIDE AMINE); EDITING TECHNOLOGIES; CHOLINERGIC SYSTEM; EFFICIENT; THERAPY; PROLIFERATION; POLYSACCHARIDE
Issue Date
2015-05
Publisher
WILEY-V C H VERLAG GMBH
Citation
SMALL, v. 11, Page. 2069-2079
Abstract
Stem cells are poorly permissive to non-viral gene transfection reagents. In this study, we explored the possibility of improving gene delivery into human embryonic (hESC) and mesenchymal (hMSC) stem cells by synergizing the activity of a cell-binding ligand with a polymer that releases nucleic acids in a cytoplasm-responsive manner. A 29 amino acid long peptide, RVG, targeting the nicotinic acetylcholine receptor (nAchR) was identified to bind both hMSC and H9-derived hESC. Conjugating RVG to a redox-sensitive biodegradable dendrimer-type arginine-grafted polymer (PAM-ABP) enabled nanoparticle formation with plasmid DNA without altering the environment-sensitive DNA release property and favorable toxicity profile of the parent polymer. Importantly, RVG-PAM-ABP quantitatively enhanced transfection into both hMSC and hESC compared to commercial transfection reagents like Lipofectamine 2000 and Fugene. similar to 60% and 50% of hMSC and hESC were respectively transfected, and at increased levels on a per cell basis, without affecting pluripotency marker expression. RVG-PAM-ABP is thus a novel bioreducible, biocompatible, non-toxic, synthetic gene delivery system for nAchR-expressing stem cells. Our data also demonstrates that a cell-binding ligand like RVG can cooperate with a gene delivery system like PAM-ABP to enable transfection of poorly-permissive cells.
URI
http://onlinelibrary.wiley.com/doi/10.1002/smll.201402933/abstracthttp://hdl.handle.net/20.500.11754/24822
ISSN
1613-6810; 1613-6829
DOI
http://dx.doi.org/10.1002/smll.201402933
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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