Gene delivery to in situ veins: Differential effects of adenovirus and adeno-associated viral vectors
| Autor: | Kurt K. Rhynhart, Sidhu P. Gangadharan, Michael S. Conte, Mohammad H. Eslami, Richard O. Snyder, XinXin Sui |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
0303 health sciences
business.industry Genetic enhancement Transfection 030204 cardiovascular system & hematology Gene delivery medicine.disease_cause Virology Molecular biology Viral vector Adenoviridae 03 medical and health sciences Titer 0302 clinical medicine Gene expression medicine Surgery Cardiology and Cardiovascular Medicine business Ex vivo 030304 developmental biology |
| Zdroj: | Journal of Vascular Surgery. 31:1149-1159 |
| ISSN: | 0741-5214 |
| DOI: | 10.1067/mva2000.106951 |
| Popis: | Purpose: Gene transfer offers the potential to modify vein graft biology at the time of surgical implantation. Efficiency of gene delivery, stability of expression, and host responses are critical parameters for candidate vectors. We compared the effects of intraluminal exposure with adenovirus (AD) and adeno-associated virus (AAV) vectors on transgene expression and monocyte adhesion (MA) in treated vein segments. Methods: Adult New Zealand white rabbits (N = 51) were anesthetized, and the jugular veins were cannulated bilaterally. Veins were gently distended with either vector (2·108 to 1·1010 infective particles/mL) or vehicle (control) for 30 minutes, after which venous flow was restored. AD and AAV vectors encoding for the marker genes β-galactosidase (LacZ) and green fluorescent protein (GFP) were used. Vessels were explanted 2 to 40 days postinfection for analysis of gene expression (X-gal staining, reverse transcriptase-polymerase chain reaction), MA, and immunohistochemistry. Ex vivo adhesion assays used 51Cr-labeled THP-1 cells. Statistical significance was tested by using analysis of variance with a P value less than.05. Results: All animals survived, and all treated veins were patent at sacrifice. Intraluminal exposure to AD at a titer of 1·109 resulted in near complete transduction of the endothelium at 2 days, with no detectable expression by day 14. At an equal titer of infectious particles, transgene expression was markedly less for AAV at 2 to 7 days, but improved at 2 weeks and persisted to 40 days. MA was significantly increased 2 days after AD exposure (2.7-fold vs control, *P |
| Databáze: | OpenAIRE |
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