Adeno-Associated Viral Vectors for Gene Transfer and Gene Therapy

Abstract

Adeno-associated virus (AAV) is

Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord

“…17 Long-term expression of transgenes in tissues after AAV vector transduction, including the spinal cord, 18 has been documented for periods of at least 18 months. 19,20 Transgene expression after AAV infection can induce a variety of cell-specific changes in the host genome, [21][22][23] including morphological changes related to reversal of defective CNS degeneration or behavior 21,23 by the presence of the transgene 24,25 such as BDNF.…”

Recombinant adeno-associated virus vector-transduced vascular endothelial cells express the thrombomodulin transgene under the regulation of enhanced plasminogen activator inhibitor-1 promoter

“…Moreover, down-regulation of a viral promoter may take place in vivo. 12 For an ideal gene therapy, timely expression of transgenes at the specific site may be required. PAI-1 expression is restricted to vascular cells and adipocytes under physiological conditions 19,33 and is up-regulated by a variety of molecules including TGFβ1, inflammatory cytokines, and bacterial endotoxins.…”

“…In addition to the TM gene, a variety of genes can be expressed in vascular endothelial cells using our system. Since topical administration of rAAV vectors is more effective than an intravenous injection for transduction of cells, [10][11][12] transcatheter injection of recombinant AAV vectors at specific sites may be suitable for this purpose. Another clinical application of this system may be ex vivo transduction of vascular endothelial cells of surgically removed vessels, such as the saphenous vein used in coronary artery bypass grafting, to express the TM gene.…”

“…Another attractive feature of rAAV is their low immunogenecity (see reviews, Refs 10-12). A variety types of cultured cells [10][11][12] including vascular smooth muscle cells 13 could be transduced by rAAV vectors in vitro. Therefore, we constructed rAAV vectors which contained the human TM gene driven by the enhanced PAI-1 promoter for transduction of vascular endothelial cells for thrombomodulin transgene expression in vitro and in vivo.…”

Recombinant adeno-associated virus mediated gene transfer in a mouse model for homocystinuria

“…rAAV is a promising vector for gene therapy because of its stability in the long-term expression of transgene products that have relatively weak immune responses (Snyder et al, 1997;Halbert et al, 2000). Numerous in vivo studies have demonstrated that recombinant AAV-2 vectors can efficiently transduce many tissues and lead to stable gene expression (Bueler et al, 1999;Snyder, 1999). AAV vectors have been widely used in gene therapy studies in inherited diseases such as hemophilia B (Kay et al, 2000;Manno et al, 2003), cystic fibrosis (CF) (Flotte et al, 2003), and Fabry disease (Takahashi et al, 2002) with promising results.…”