Immobilization of gene vectors on polyurethane surfaces using a monoclonal antibody for localized gene delivery.
BACKGROUND
Conventional strategies of gene therapy using viral vectors result in suboptimal localization and potentially dangerous distal spread of vector. We hypothesized that localized delivery of adenoviral gene vectors could be achieved from a polyurethane (PU) film through a mechanism involving anti-viral antibody tethering.


METHODS
PU films were formulated with a collagen coating. Anti-adenoviral monoclonal antibodies were covalently bound to the collagen surface. These antibodies enabled tethering of replication-defective adenoviruses [Ad-GFP (encoding green fluorescent protein)] through highly specific antigen-antibody affinity. The binding stability and in vitro delivery of virus bound on PU films were investigated. Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the PU matrix. In vivo experiments with collagen-coated PU films investigated atrial epicardial implant and subdermal implant models in Yorkshire swine.


RESULTS
We report for the first time successful PU film-based gene delivery using antibody-tethered adenovirus encoding the green fluorescent protein (GFP), demonstrating efficient and highly localized gene delivery to arterial smooth muscle cells in cell culture and pig implant. In comparison, direct injections of viral vectors into subcutaneous sites gave sparse, needle-track-oriented GFP expression patterns.


CONCLUSIONS
We conclude that PU film is a suitable platform for a localizable viral vector delivery system that also prevents systemic spread of vector. Gene delivery using PU film-based anti-viral antibody tethering of vectors should be suitable for a wide array of single or multiple therapeutic gene strategies, and for further device-based gene delivery therapeutic strategies.
Mei
Lin
L
Institute of Biomedical Engineering, Peking Union Medical College, Chinese Academy of Medical Sciences, The Tianjin Key Laboratory of Biomaterial Research, Tianjin 300192, China.
Jin
Xu
X
Song
Cunxian
C
Wang
Manyan
M
Levy
R J
RJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D010496:Pericardium / Q000166:cytology; D011140:Polyurethanes / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D013388:Succinimides / Q000737:chemistry; D013552:Swine; D014230:Triazoles / Q000737:chemistry
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D011140:Polyurethanes; D013388:Succinimides; D014230:Triazoles; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; D003094:Collagen