Journal article
Adenovirus-Mediated Transfer of the CFTR Gene to Lung of Nonhuman Primates: Biological Efficacy Study
Human gene therapy, Vol.4(6), pp.759-769
12/1993
DOI: 10.1089/hum.1993.4.6-759
PMID: 7514445
Abstract
We have evaluated the biological efficacy of E1-deleted adenoviruses in baboons for lung-directed gene therapy of cystic fibrosis (CF). The experimental design attempted to simulate a phase I clinical trial with animals receiving a single dose of virus to an isolated pulmonary segment. A total of 14 animals divided into four groups, each of which received escalating doses of virus, were used. Individual animals were necropsied 4 and 21 days after gene transfer and tissues were carefully surveyed for gene expression. Expression of the transgene was localized primarily to the area into which it was infused; the efficiency of recombinant gene expression and the abundance of transgene sequences were proportional to dose and both diminished with time. Transgene expression was found predominantly in alveolar cells with patches of expression in the proximal and distal airway. Analysis of adenoviral protein expression within transgene-expressing cells revealed infrequent expression of the E2a gene and no detectable expression of late genes (i.e., fiber protein). These results suggest that recombinant adenovirus can be used to transfer genes efficiently to the lung of nonhuman primates and that therapeutic strategies of cystic fibrosis may require repetitive administration with current vectors.
Details
- Title: Subtitle
- Adenovirus-Mediated Transfer of the CFTR Gene to Lung of Nonhuman Primates: Biological Efficacy Study
- Creators
- John F. Engelhardt - The Wistar InstituteRichard H. Simon - Internal Medicine - Pulmonary/Critical CareYiping Yang - University of PennsylvaniaMonica Zepeda - University of PennsylvaniaSara Weber-Pendleton - University of MichiganBenjamin Doranz - University of PennsylvaniaMariann Grossman - University of PennsylvaniaJames M. Wilson - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Human gene therapy, Vol.4(6), pp.759-769
- DOI
- 10.1089/hum.1993.4.6-759
- PMID
- 7514445
- NLM abbreviation
- Hum Gene Ther
- ISSN
- 1043-0342
- eISSN
- 1557-7422
- Language
- English
- Date published
- 12/1993
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284349902771
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