Gene therapy, 2008-08, Vol.15 (16), p.1167-1175
2008
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- Autor(en) / Beteiligte
- Titel
- Lentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expression
- Ist Teil von
- Gene therapy, 2008-08, Vol.15 (16), p.1167-1175
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2008
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Gene transfer for cystic fibrosis (CF) airway disease has been hampered by the lung's innate refractivity to pathogen infection. We hypothesized that early intervention with an integrating gene transfer vector capable of transducing the lung via the lumen may be a successful therapeutic approach. An HIV-based lentiviral vector pseudotyped with the baculovirus gp64 envelope was applied to the fetal, neonatal or adult airways. Fetal intra-amniotic administration resulted in transduction of approximately 14% of airway epithelial cells, including both ciliated and non-ciliated epithelia of the upper, mid and lower airways; there was negligible alveolar or nasal transduction. Following neonatal intra-nasal administration we observed significant transduction of the airway epithelium (approximately 11%), although mainly in the distal lung, and substantial alveolar transduction. This expression was still detectable at 1 year after application. In the adult, the majority of transduction was restricted to the alveoli. In contrast, vesicular stomatitis virus glycoprotein pseudotyped virus transduced only alveoli after adult and neonatal application and no transduction was observed after fetal administration. Repeat administration did not increase transduction levels of the conducting airway epithelia. These data demonstrate that application at early developmental stages in conjunction with an appropriately pseudotyped virus provides efficient, high-level transgene expression in the murine lung. This may provide a modality for treatment for lung disease in CF.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0969-7128eISSN: 1476-5462DOI: 10.1038/gt.2008.74Titel-ID: cdi_proquest_miscellaneous_69390869
- Format
- –
- Schlagworte
- Allergic diseases, Alveoli, Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy, Animals, Animals, Newborn, Applied cell therapy and gene therapy, Baculoviridae - genetics, Baculovirus, Biological and medical sciences, Biomedical and Life Sciences, Biomedicine, Biotechnology, Care and treatment, Cell Biology, Cystic fibrosis, Cystic Fibrosis - metabolism, Cystic Fibrosis - therapy, Developmental stages, Epithelial cells, Epithelium, Female, Fetuses, Fundamental and applied biological sciences. Psychology, Gene Expression, Gene Therapy, Gene transfer, Genetic aspects, Genetic Therapy - methods, Genetic Vectors - administration & dosage, Genetic Vectors - genetics, Glycoprotein gp64, Green Fluorescent Proteins - analysis, Green Fluorescent Proteins - genetics, Health aspects, Health. Pharmaceutical industry, HIV, HIV - genetics, Human Genetics, Human immunodeficiency virus, Immunohistochemistry, Industrial applications and implications. Economical aspects, Intranasal administration, Lentivirus, Luciferases - analysis, Luciferases - genetics, Lung - growth & development, Lung - metabolism, Lung diseases, Lungs, Male, Medical sciences, Mice, Mice, Inbred Strains, Models, Animal, Nanotechnology, Neonates, original-article, Refractivity, Respiratory agents, Respiratory tract diseases, Rodents, Stomatitis, Time, Transduction, Transduction, Genetic - methods, Transfusions. Complications. Transfusion reactions. Cell and gene therapy, Transgenes, Vesicular stomatitis virus, Viral Envelope Proteins - genetics, Viruses