Cationic polymer and lipids augment adenovirus-mediated gene transfer to cerebral arteries in vivo.
Adenovirus-mediated gene transfer to blood vessels is relatively inefficient because binding of adenovirus to vessels is limited. The authors have reported that incorporation of cationic polymer and lipids with adenovirus augments gene transfer to blood vessels ex vivo. In this study, the authors determined whether complexes of adenovirus and cations improve efficiency of gene transfer in vivo. Poly-L-lysine, lipofectamine, or lipofectin was complexed with adenovirus encoding beta-galactosidase. Optimum ratios of the cations per adenovirus were determined by gene transfer to fibroblasts. After injection of the adenovirus into the cisterna magna of anesthetized rabbits, transgene activity was greater in the adventitia of intracranial arteries and meninges after injection of the complexes than adenovirus alone. Thirty minutes after application of adenovirus with the cations, binding of adenovirus to fibroblast cells in vitro or the basilar artery in vivo (by Southern blot analysis) was augmented, which suggests that enhanced binding of virus contributes to augmentation of transgene expression. Thus, cationic polymer and lipids improve transgene expression in intracranial arteries, primarily in the adventitia, after adenovirus-mediated gene transfer in vivo. This strategy may be applicable to studies of gene transfer and eventually for gene therapy.
Toyoda
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K
Department of Internal Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242, USA.
Nakane
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Heistad
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D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001488:Basilar Artery / Q000502:physiology*; D015139:Blotting, Southern; D002946:Cisterna Magna; D015870:Gene Expression; D018014:Gene Transfer Techniques; D020404:Glycerophospholipids / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D010714:Phosphatidylethanolamines; D011817:Rabbits; D013096:Spermine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D019076:Transgenes / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; C098223:2,3-dioleyloxy-N-(2-(sperminecarboxamido)ethyl)-N,N-dimethyl-1-propanaminium trifluoroacetate; D020404:Glycerophospholipids; D010714:Phosphatidylethanolamines; D013096:Spermine; D001616:beta-Galactosidase