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Gene transfer into vascular cells using adeno-associated virus (AAV) vectors
Y Maeda1, U Ikeda, Y Ogasawara
1Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Cardiovascular Research
|January 31, 1998
Summary
Adeno-associated virus (AAV) vectors efficiently transduce rat vascular smooth muscle cells in vitro. Ex vivo studies show AAV vectors target endothelial and adventitial cells in aortas, suggesting promise for cardiovascular gene therapy.
Area of Science:
- Molecular Biology
- Gene Therapy
- Cardiovascular Research
Background:
- Adeno-associated virus (AAV) vectors are nonpathogenic parvoviruses with potential for gene therapy.
- AAV vectors offer long-term transgene expression and can transduce non-dividing cells.
Purpose of the Study:
- To evaluate adeno-associated virus (AAV) vector-mediated gene transfer into rat vascular smooth muscle cells (VSMC) in vitro.
- To assess ex vivo gene transfer into rat thoracic aortas using AAV vectors.
Main Methods:
- Transduction of cultured rat VSMC and excised rat aortas with AAV vector carrying the beta-galactosidase gene (lacZ).
- Evaluation of beta-galactosidase (beta-gal) expression using X-gal staining and ELISA at various multiplicities of infection (MOI).
Main Results:
- In vitro, AAV-lacZ transduction of VSMC increased with MOI, reaching up to 50% positive cells and detectable expression for at least 1 month.
- Ex vivo, AAV vectors transduced endothelial and adventitial cells in rat aortic segments, but not medial VSMC.
Conclusions:
- AAV vectors demonstrate efficient in vitro transduction of rat VSMC.
- Ex vivo gene transfer using AAV vectors targets aortic endothelial and adventitial cells, not medial VSMC.
- AAV-based vectors show promise for cardiovascular gene therapy applications.