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Publication Detail
Factors influencing adenovirus-medated airway transduction in fetal mice
  • Publication Type:
    Journal article
  • Publication Sub Type:
    JOUR
  • Authors:
    Buckley SMK, Waddington SN, Jezzard S, Lawrence L, Schneider H, Themis M, Coutelle C
  • Publication date:
    2005
  • Pagination:
    484, 492
  • Volume:
    12
  • Issue:
    3
  • Notes:
    Intra-amniotic injection of adenovirus allows transduction of the fetal airways following natural fetal breathing movements. This administration method is promising for use in gene therapy for cystic fibrosis and other diseases where the main target for exogenous gene expression is the lung. Here, we have investigated factors that may affect the efficacy of gene transfer to the murine fetal lung. We examined marker compound distribution and transgene expression (from a first generation adenoviral vector) at different stages of development. This demonstrated that fetal breathing movements at 15-16 days of gestation are of sufficient intensity to carry marker/vector into the fetal lungs. These movements can be significantly stimulated by the combination of intra-amniotic theophylline administration and post-operative exposure of the dam to elevated CO2 levels. However, the most important factor for efficient and consistent pulmonary transgene delivery is the dose of adenoviral vector used, as both the degree of transduction and the percentage of lungs transduced increases with escalating viral dose.
Abstract
Intra-amniotic injection of adenovirus allows transduction of the fetal airways following natural fetal breathing movements. This administration method is promising for use in gene therapy for cystic fibrosis and other diseases where the main target for exogenous gene expression is the lung. Here, we have investigated factors that may affect the efficacy of gene transfer to the murine fetal lung. We examined marker compound distribution and transgene expression (from a first generation adenoviral vector) at different stages of development. This demonstrated that fetal breathing movements at 15-16 days of gestation are of sufficient intensity to carry marker/vector into the fetal lungs. These movements can be significantly stimulated by the combination of intra-amniotic theophylline administration and post-operative exposure of the dam to elevated CO2 levels. However, the most important factor for efficient and consistent pulmonary transgene delivery is the dose of adenoviral vector used, as both the degree of transduction and the percentage of lungs transduced increases with escalating viral dose.
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