Calcium phosphate precipitates augment adenovirus-mediated gene transfer to blood vessels in vitro and in vivo

K TOYODA; J. J ANDRESEN; J ZABNER; F. M FARACI; D. D HEISTAD

doi:10.1038/sj.gt.3301214

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Calcium phosphate precipitates augment adenovirus-mediated gene transfer to blood vessels in vitro and in vivo

Journal article

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Calcium phosphate precipitates augment adenovirus-mediated gene transfer to blood vessels in vitro and in vivo

K TOYODA, J. J ANDRESEN, J ZABNER, F. M FARACI and D. D HEISTAD

Gene therapy, Vol.7(15), pp.1284-1291

2000

DOI: 10.1038/sj.gt.3301214

PMID: 10918499

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Abstract

Adenovirus (Ad)-mediated gene transfer to blood vessels is relatively inefficient, probably because binding of adenovirus to the endothelium and adventitia seems to be limited. Association of calcium phosphate (CaPi) precipitates with adenovirus improves efficiency of gene transfer to some cells in culture and to mouse lung in vivo. In this study, we tested the hypothesis that CaPi is useful for adenovirus-mediated gene transfer to blood vessels. In fibroblast and endothelial cells in culture, Ad:CaPi coprecipitates greatly increased transgene expression. Ad:CaPi also enhanced transgene expression in both adventitia and endothelium of carotid arteries and aortae from rabbits studied ex vivo. After injection of Ad:CaPi into the cisterna magna of rabbits in vivo, the transgene product was markedly increased in leptomeninges of the ventral brain stem, including the adventitia of the basilar artery. We also examined mechanisms of enhanced gene transfer. Binding of adenovirus to fibroblast and endothelial cells in culture, and to the basilar artery in vivo, as determined using Southern blot analysis, was augmented by CaPi. Antibody to adenoviral fiber knob did not inhibit augmented transgene expression by Ad:CaPi. The finding suggests that improved adenoviral binding occurs primarily via a fiber-independent pathway. Thus, CaPi precipitates are useful for improvement of adenovirus-mediated gene transfer to blood vessels in vitro and in vivo.

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Details

Title: Subtitle: Calcium phosphate precipitates augment adenovirus-mediated gene transfer to blood vessels in vitro and in vivo
Creators: K TOYODA - Department of Internal Medicine, Pharmacology, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa, United States
J. J ANDRESEN - Department of Internal Medicine, Pharmacology, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa, United States
J ZABNER - Department of Physiology and Biophysics, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa, United States
F. M FARACI - Department of Internal Medicine, Pharmacology, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa, United States
D. D HEISTAD - Department of Internal Medicine, Pharmacology, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Gene therapy, Vol.7(15), pp.1284-1291
DOI: 10.1038/sj.gt.3301214
PMID: 10918499
NLM abbreviation: Gene Ther
ISSN: 0969-7128
eISSN: 1476-5462
Publisher: Nature Publishing Group; Basingstoke
Language: English
Date published: 2000
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040292902771

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