Biomaterial-mediated retroviral gene transfer using self-assembled monolayers

被引:28
作者
Gersbach, Charles A.
Coyer, Sean R.
Le Doux, Joseph M.
Garcia, Andres J.
机构
[1] Georgia Inst Technol, George W Woodruff Sch Mech Engn, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA
[2] Emory Univ, Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA
[3] Georgia Inst Technol, Georgia Tech Emory Ctr Engn Living Tissue, Atlanta, GA 30332 USA
关键词
fibroblast; genetic engineering; gene therapy; gene transfer; self-assembly; alkanethiol;
D O I
10.1016/j.biomaterials.2007.07.047
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Biomaterial-mediated gene delivery has recently emerged as a promising alternative to conventional gene transfer technologies that focus on direct delivery of viral vectors or DNA-polymer/matrix complexes. However, biomaterial-based strategies have primarily targeted transient gene expression vehicles, including plasmid DNA and adenovirus particles. This study expands on this work by characterizing biomaterial properties conducive to the surface immobilization of retroviral particles and subsequent transduction of mammalian cells at the cell-material interface. Self-assembled monolayers (SAMs) of functionally-terminated alkanethiols on gold were used to establish biomaterial surfaces of defined chemical composition. Gene transfer was observed to be greater than 90% on NH2-terminated surfaces, approximately 50% on COOH-functionalized surfaces, and undetectable on CH3-terminated SAMs, similar to controls of tissue culture-treated polystyrene. Gene delivery via the NH2-SAM was further characterized as a function of retrovirus coating time, virus concentration, and cell seeding density. Finally, SAM-mediated gene delivery was comparable to fibronectin- and poly-L-lysine-based methods for gene transfer. This work is significant to establishing safe and effective gene therapy strategies, developing efficient methods for gene delivery, and supporting recent progress in the field of biomaterial-mediated gene transfer. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5121 / 5127
页数:7
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