A bio-recognition device developed onto nano-crystals of carbonate apatite for cell-targeted gene delivery.
The DNA delivery to mammalian cells is an essential tool for analyzing gene structure, regulation, and function. The approach holds great promise for the further development of gene therapy techniques and DNA vaccination strategies to treat and control diseases. Here, we report on the establishment of a cell-specific gene delivery and expression system by physical adsorption of a cell-recognition molecule on the nano-crystal surface of carbonate apatite. As a model, DNA/nano-particles were successfully coated with asialofetuin to facilitate uptake by hepatocyte-derived cell lines through the asialoglycoprotein receptor (ASGPr) and albumin to prevent non-specific interactions of the particles with cell-surface. The resulting composite particles with dual surface properties could accelerate DNA uptake and enhance expression to a notable extent. Nano-particles coated with transferrin in the same manner dramatically enhanced transgene expression in the corresponding receptor-bearing cells and thus our newly developed strategy represents a universal phenomenon for anchoring a bio-recognition macromolecule on the apatite crystal surface for targeted gene delivery, having immediate applications in basic research laboratories and great promise for gene therapy.
Chowdhury
E H
EH
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Akaike
Toshihiro
T
D000818:Animals; D001031:Apatites / Q000737:chemistry*; D001212:Asialoglycoproteins / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D060748:Fetuins; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000737:chemistry
D001031:Apatites; D001212:Asialoglycoproteins; D060748:Fetuins; D014168:Transferrin; D000509:alpha-Fetoproteins; C017029:asialofetuin; C030782:carboapatite; D004247:DNA; D008156:Luciferases