Adeno-associated virus expression systems for gene transfer

Persistent expression of canine factor IX in hemophilia B canines

“…rAAV is nonpathogenic and has a broad cell range of infection. 9 The vector capsid is comprised of primarily one major polypeptide (Vp3) 10 and does not elicit a cell-mediated immunologic response. [11][12][13] The packaging restriction of the 4.6 kb AAV genome 14,15 limits the use of large cDNAs.…”

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

“…29 These transfection systems have benefits over viral carriers in that DNA size is less restricted and there is minimal immunogenicity and toxicity. 6,30,31 All of these viral vectors have the potential for the regeneration of wild-type, replication-competent strains and have, at some point, been associated with or caused death. [32][33][34][35] These risks are especially problematic in patients with ischemic cardiomyopathy who may ultimately need a cardiac transplant and will require chronic immunosuppression.…”

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

“…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.…”