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In utero gene transfer into the pulmonary epithelium

Nature Medicine volume 1, pages 1201–1203 (1995)Cite this article

Abstract

In early gestation the internal surface of the lung is structurally simple and an ideal target for somatic gene transfer1–3. The transfer of genes into the growing lung would be particularly useful in the prenatal correction of cystic fibrosis, which has devastating pulmonary complications. In addition, in utero gene therapy has the potential to immunotolerize the individual, and thereby to avoid the immune reactions now seen with the current generation of adenoviral vectors4,5. We injected a replication-defective adenoviral vector containing the lacZ reporter gene (Ad5.CMVlacZ) into the amniotic fluid of rat pups on the 16th day of gestation6–9. At 16 days of gestation, rat lungs are equivalent in maturity to those of a 22-week human fetus as their airways are lined with undifferentiated multipotential stem cells. The pups showed high-level reporter gene expression in their airways a week following birth (13 days following infection). The expression was maintained during a time when the lung volume increased approximately 20-fold, alveolarization occurred, and the epithelial cells differentiated2,3. These data establish gene targeting of undifferentiated fetal cells as an effective means of gene therapy.

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Authors and Affiliations

  1. Pediatric Pulmonology, Tulane University Medical Center and Laboratory of Molecular Genetics, Alton Ochsner Medical Foundation, 1516 Jefferson Highway, New Orleans, Louisiana, 70121, USA

    Harmanjatinder S. Sekhon & Janet E. Larson

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  1. Harmanjatinder S. Sekhon
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  2. Janet E. Larson
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Sekhon, H., Larson, J. In utero gene transfer into the pulmonary epithelium. Nat Med 1, 1201–1203 (1995). https://doi.org/10.1038/nm1195-1201

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