Abstract:
:Approaches to alter the native tropism of adenoviruses (Ads) are beneficial to increase their efficacy and safety profile. Liver tropism is important with regard to potential clinical toxicity in humans. Ad5/3 chimeras in which the Ad5 knob is substituted by the Ad3 knob, such as Ad5/3luc1, have been recently shown to increase infectivity of ovarian cancer cell lines and primary tumor cells, which express low levels of the coxsackie-adenovirus receptor (CAR), without increasing infectivity of liver cells. A novel strategy to address the problem of liver uptake and improve the tumor/liver ratio is genetic replacement of the Ad fiber shaft. Ad5.Ad3.SH.luc1 is an Ad5-based vector that contains the fiber shaft from Ad serotype 3 but the fiber knob from Ad serotype 5. To compare tumor/liver of Ad5.Ad3.SH.luc1 and Ad5/3luc1 in vivo, we created three different tumor and treatment models of ovarian cancer in mice, simulating intraperitoneal and intravenous administration of tumors. Ad5.Ad3.SH.luc1 displayed the lowest liver tropism of all viruses in all models tested. Intravenous administration of all viruses resulted in higher tumor transduction rates compared to intraperitoneal administration. Genetic shortening of the Ad5 fiber shaft significantly increases relative tumor/liver gene transfer. This could improve the effective tumor dose and reduce side effects, thereby increasing the bioavailability of therapeutic agents.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Breidenbach M,Rein DT,Wang M,Nettelbeck DM,Hemminki A,Ulasov I,Rivera AR,Everts M,Alvarez RD,Douglas JT,Curiel DTdoi
10.1089/10430340460745829keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
509-18issue
5eissn
1043-0342issn
1557-7422journal_volume
15pub_type
杂志文章abstract::Previously, we described a nonviral cytoplasmic gene therapy vector system based on the T7 autogene concept. This system has been shown to achieve rapid and high levels of gene expression in a variety of animal cells and tissues. To test the utility of the system in vivo tumor ablation, a T7 cancer gene therapy plasmi...
journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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pub_type: 杂志文章
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pub_type: 杂志文章,多中心研究
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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