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

Authors
 Jagadish Beloor  ;  Suresh Ramakrishna  ;  Kihoon Nam  ;  Chang Seon Choi  ;  Jongkil Kim  ;  Sung Hwa Kim  ;  Hyong Jin Cho  ;  HeungSoo Shin  ;  Hyongbum Kim  ;  Sung Wan Kim  ;  Sang-Kyung Lee  ;  Priti Kumar 
Citation
 SMALL, Vol.11(17) : 2069-2079, 2015 
Journal Title
 SMALL 
ISSN
 1613-6810 
Issue Date
2015
MeSH
Animals ; Arginine/chemistry ; Biocompatible Materials/chemistry* ; Cytoplasm/metabolism ; DNA/chemistry ; Embryonic Stem Cells/cytology ; Fibroblasts/metabolism ; Flow Cytometry ; Gene Transfer Techniques* ; Genetic Vectors/chemistry* ; Green Fluorescent Proteins/chemistry ; Humans ; Ligands ; Lipids/chemistry ; Mesenchymal Stromal Cells/cytology ; Mice ; Oxidation-Reduction ; Peptides/chemistry* ; Phenotype ; Plasmids/metabolism ; Polymers/chemistry ; Receptors, Nicotinic/metabolism ; Stem Cells/cytology* ; Transfection
Keywords
bioreducible polymer ; cell-binding ligand ; embryonic stem cells ; mesenchymal stem cells ; non-viral gene delivery
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. ∼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.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/smll.201402933/full
DOI
10.1002/smll.201402933
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyongbum(김형범) ORCID logo https://orcid.org/0000-0002-4693-738X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141474
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