Referenced in: none

Automatically associated channels: Kv10.1

Title: 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

Journal, date & volume: Small, 2015 May 6 , 11, 2069-79

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25515928

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.