(NAS Colloquium) Genetic Engineering of Viruses and Viral Vectors (1996) / Chapter Skim
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Fusigenic viral liposome for gene therapy in cardiovascular diseases
Fusigenic viral liposome for gene therapy in cardiovascular diseases
Pages 11421-11425
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From page 11421... ...
In the cardiovascular system, we have documented successful cytostatic gene ther apy in models of vascular proliferative disease using antisense oligodeoxynucleotides against cell cycle genes, double stranded oligodeoxynucleotides as "decoys" to trap the tran scription factor E2F, and expression of a transgene encoding the constitutive endothelial cell form of nitric oxide synthase. Similar strategies are also effective for the genetic engineering of vein grafts and for the treatment of a mouse model of immune-mediated glomerular disease.
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From page 11422... ...
When AS ODN to basic fibroblast growth factor was transfected into VSMCs using HVJ-liposomes and compared with cationic lipid transfection or direct ODN transfer without any vector, the concentration of AS basic fibroblast growth factor required to reduce cellular DNA synthesis by 75~o was approximately 0.1 ~M, 10 ,uM, and 20 ,uM, respectively (21~. Thus, the HVJ-liposome is an effective method for ODN and plasmid DNA transfer.
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From page 11423... ...
Our observation that the interstitium of the tunica media is stained upon incubation with liposomes without HVJ containing Evans blue dye suggests that this penetrating ability is conferred primarily by the liposome. Subsequent cell fusion and intracellular delivery of DNA is mediated by HVJ fusion proteins.
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From page 11424... ...
Although several factors are known to stimulate endothelial cell growth, we have recently found that hepatocyte growth factor is a more potent accelerator of endothelialization than either vascular endothelial cell growth factor or basic fibroblast growth factor. In addition, unlike basic fibroblast growth factor, hepatocyte growth factor does not stimulate VSMC growth.
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From page 11425... ...
Colloquium Paper: Dzau et al.
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