| In situ retrovirus-mediated gene transfer into dog liver. | |
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MedLine Citation:
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PMID: 8399488 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dogs were used as a large animal model to assess the feasibility and safety of a surgical method for gene transfer into hepatocytes in vivo. This method, which we previously described in rats, consists of a partial hepatectomy aimed at inducing liver regeneration, followed by the selective in situ perfusion of the remnant liver parenchyma with a retrovirus preparation. Isolation of the liver was obtained by clamping the afferent and efferent blood vessels, a procedure that prevented retroviral vector dissemination and genetic modification of nonhepatic organs. A helper-free retrovirus vector encoding beta-galactosidase targeted to the nucleus was perfused in the liver of 5 golden retriever dogs. Volumes up to 1,650 ml of fresh or concentrated vector stocks were perfused and the procedure was well tolerated. Gene transfer, observed in 3 of 5 treated dogs when documented on liver biopsy fragments obtained at day 4, involved 0.15-0.6% hepatocytes and persisted at equivalent levels at the time of sacrifice, 6 weeks later. No propagation of the vector to other tissues was detected. These observations suggest that the selective perfusion of the regenerating liver might be considered an alternative to liver transplantation for the treatment of certain severe genetic liver disorders, or for the delivery of a therapeutic protein into the serum. |
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Authors:
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J E Cardoso; S Branchereau; P R Jeyaraj; D Houssin; O Danos; J M Heard |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Human gene therapy Volume: 4 ISSN: 1043-0342 ISO Abbreviation: Hum. Gene Ther. Publication Date: 1993 Aug |
Date Detail:
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Created Date: 1993-11-23 Completed Date: 1993-11-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9008950 Medline TA: Hum Gene Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 411-8 Citation Subset: IM |
Affiliation:
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Laboratoire de Recherche Chirurgicale, Faculté de Médecine Cochin-Port Royal, Paris, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Cells, Cultured DNA Dogs Feasibility Studies Female Gene Transfer Techniques* Genetic Vectors Liver / metabolism*, surgery Male Molecular Sequence Data Polymerase Chain Reaction Retroviridae / genetics* |
| Chemical | |
Reg. No./Substance:
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9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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