| In utero gene delivery by intraamniotic injection of a retroviral vector producer cell line in a nonhuman primate model. | |
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MedLine Citation:
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PMID: 11589828 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In utero gene therapy (IUGT) offers the promise of treating a wide variety of genetic diseases before the development of disease manifestations. The most convenient and potentially easiest method of targeting the fetus is through injection into the amniotic cavity. For long-term correction of genetic defects, retroviral vectors have great potential as a tool for gene therapy strategies. However, retroviral vectors are limited by growth to low titers. In an attempt to increase the amount of vector particles delivered and assess the potential of intraamniotic administration, we injected a retroviral vector producer cell line encoding the lacZ gene into the amniotic fluid of a nonhuman primate model. After birth the infants were analyzed for vector-mediated transduction. Two of four fetuses were successfully transduced, with transgene expression detected in the esophagus, trachea, and stomach. In some sections of tissue, nearly 100% of the cells lining the lumen of these tissues were positive for transduction. Although successful, the limited number of tissues in which transduction was observed led to an in vitro analysis of the effects of amniotic fluid (AF). The presence of amniotic fluid inhibited transduction by 99%. AF affected both the transducing activity of the vector and the health of the packaging cells. The negative effects of AF were gestational age dependent; greater inhibition was observed from AF collected at later stages of pregnancy. The fact that transduction was successful despite these negative effects indicates that this approach is a promising strategy for gene therapy. |
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Authors:
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M Bennett; H Galan; G Owens; R Dewey; R Banks; J Hobbins; F Accurso; J Schaack |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Human gene therapy Volume: 12 ISSN: 1043-0342 ISO Abbreviation: Hum. Gene Ther. Publication Date: 2001 Oct |
Date Detail:
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Created Date: 2001-10-08 Completed Date: 2001-12-07 Revised Date: 2007-11-14 |
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: 1857-65 Citation Subset: IM |
Affiliation:
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Department of Microbiology, School of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Amniotic Fluid* Animals Cell Line Esophagus / embryology Female Galactosides / metabolism Gene Transfer Techniques* Genetic Vectors Gestational Age Immunohistochemistry Indoles / metabolism Lac Operon Macaca Mice Polymerase Chain Reaction Pregnancy Retroviridae / genetics* Stomach / embryology Time Factors Trachea / embryology Transduction, Genetic Transgenes |
| Grant Support | |
ID/Acronym/Agency:
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1K12HD01271-01A1/HD/NICHD NIH HHS; R01 HL58344/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Galactosides; 0/Indoles; 7240-90-6/5-bromo-4-chloro-3-indolyl beta-galactoside |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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