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Small. 2015 May 6;11(17):2069-79. doi: 10.1002/smll.201402933. Epub 2014 Dec 16.

Effective gene delivery into human stem cells with a cell-targeting Peptide-modified bioreducible polymer.

Author information

1
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, 06520, USA; Department of Bioengineering and Institute of Nano Science and Technology, Hanyang University, Seoul, 133-791, Korea.

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.

KEYWORDS:

bioreducible polymer; cell-binding ligand; embryonic stem cells; mesenchymal stem cells; non-viral gene delivery

PMID:
25515928
DOI:
10.1002/smll.201402933
[Indexed for MEDLINE]
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