Animal study of intravascular gene therapy based on polyurethane implantable devices / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the feasibility of utilizing two implantable devices made from modified polyurethane films with antibody tethered replication-defective adenoviruses encoding for green fluorescent protein (AdGFP) as gene delivery platforms.</p><p><b>METHODS</b>Intra-aortic button implants of collagen-coated polyurethane films with antibody tethered AdGFP were sutured into the infrarenal aorta of adult pigs and pulmonary valve leaflet in juvenile sheep was replaced by polyurethane pulmonary valve cusp replacement with antibody-tethered AdGFP. After seven days, the buttons, prosthetic leaflets, and their surrounding tissues were explanted and evaluated for biocompatibility and AdGFP-mediated gene transfer by fluorescent microscopy and PCR analysis.</p><p><b>RESULTS</b>In vivo analysis of gene transfer from collagen-coated polyurethane films in pig infrarenal aorta implants, one week explants of the collagen-coated polyurethane films demonstrated (14.2 +/- 2.5)% of neointimal cells on the surface of the implant. In sheep pulmonary valve leaflet replacement studies, polyurethane films with antibody tethered AdGFP vector demonstrated (25.1 +/- 5.7)% of cells attached to polyurethane valve leaflets were transduced in one week. PCR analyses showed that GFP DNA was not detectable in blood or distal tissues.</p><p><b>CONCLUSION</b>Site-specific intravascular delivery of adenoviral vectors for gene therapy can be achieved with these two kinds of polyurethane implants utilizing the antivector antibody tethering mechanism.</p>

Application of monoclonal antibody immobilized polyurethane film for site-specific gene therapy / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the feasibility of delivering viral gene vector from a collagen-coated polyurethane (PU) film through a mechanism involving monoclonal antiviral antibody tethering.</p><p><b>METHODS</b>Anti-adenoviral monoclonal antibodies were covalently bound to the collagen-coated PU surface. These antibodies enabled tethering of replication defective adenoviruses through highly specific antigen-antibody affinity. The PU film-based gene delivery using antibody-tethered adenovirus encoding green fluorescent protein (GEP) was tested in rat arterial smooth muscle cell (A10 cell) culture in vitro. The virus binding stability was studied by incubating the collagen-coated PU film in PBS solution at 37 degrees C for 20 days, followed with A10 cell cultures with the incubated films and the corresponding buffer solution.</p><p><b>RESULTS</b>PU films with antibody-tethered adenovirus encoding GFP demonstrated efficient and highly localized gene delivery to A10 cells. Virus binding was stable for at least 10 days at physiological conditions, more than 77% of the originally bound virus remained in the film after 15 day's incubation.</p><p><b>CONCLUSION</b>Gene delivery using PU film-based anti-viral antibody tethering of vectors exhibited potentials of applications in a wide array of single or multiple therapeutic gene strategies, and in further stent-based gene delivery therapeutic strategies.</p>