Endovascular microcoil gene delivery using immobilized anti-adenovirus antibody for vector tethering.
OBJECTIVE
Endovascular microcoils are widely used in interventional procedures to treat cerebral aneurysms. In the present study we report for the first time successful use of an endovascular microcoil as a gene delivery system.


METHODS
Anti-adenoviral monoclonal antibodies were covalently attached to the collagen-coated surface of either platinum or polyglycolic acid microcoils. These antibodies were used to tether replication-deficient adenovirus (Ad-GFP [encoding green fluorescent protein] or Ad-LacZ [encoding beta-galactosidase]). Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the coil. Platinum coils coated with Ad-GFP were implanted into the ligated common carotid artery (CCA) of adult rats in a model of arterial stasis and pressurization. After 7 days, CCA segments were harvested, and coils were removed for histopathology and GFP expression studies, while organs were evaluated by polymerase chain reaction to assess viral biodistribution.


RESULTS
In cell culture studies, GFP-positive smooth muscle cells were detected only on the platinum coil surface, while LacZ-positive cells were detected only on the polyglycolic acid coil surface, thus demonstrating localized gene delivery. After 7-day implantation, GFP (according to fluorescence microscopy and confirmed with immunohistochemistry) was detected on the harvested platinum coil and in the organizing thrombus within the CCA but not in the arterial wall. Morphometric analyses revealed that 13.3+2.0% of cells within the organized thrombus were transduced with Ad-GFP via the gene delivery system. However, arterial smooth muscle cells were negative for GFP according to fluorescence microscopy and immunohistochemistry. Ad-GFP was not detectable by polymerase chain reaction in lung, liver, or kidney.


CONCLUSIONS
It is concluded that catheter deployment of platinum or biodegradable gene delivery endovascular microcoils represents an interventional device-based gene therapy system that can serve as a suitable platform for either single or multiple gene therapy vectors.
Abrahams
John M
JM
Department of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pa 19104, USA.
Song
Cunxian
C
DeFelice
Suzanne
S
Grady
M Sean
MS
Diamond
Scott L
SL
Levy
Robert J
RJ
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000914:Antibodies, Viral / Q000737:chemistry* / Q000378:metabolism; D001682:Biological Availability; D019917:Blood Vessel Prosthesis Implantation; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D020099:Coated Materials, Biocompatible; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004353:Drug Evaluation, Preclinical; D004621:Embolization, Therapeutic / Q000379:methods; D015316:Genetic Therapy / Q000295:instrumentation* / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry*; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D020007:Implants, Experimental; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000737:chemistry; D008856:Microscopy, Fluorescence; D010984:Platinum / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D013927:Thrombosis / Q000378:metabolism; D014018:Tissue Distribution; D014161:Transduction, Genetic / Q000295:instrumentation / Q000379:methods; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D000914:Antibodies, Viral; D020099:Coated Materials, Biocompatible; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D011100:Polyglycolic Acid; D010984:Platinum; D001616:beta-Galactosidase