Factors influencing adenovirus-mediated airway transduction in fetal mice.
Mol Ther
; 12(3): 484-92, 2005 Sep.
Article
em En
| MEDLINE
| ID: mdl-16099411
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 for which 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 postoperative exposure of the dam to elevated CO(2) 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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traqueia
/
Adenoviridae
/
Vetores Genéticos
/
Pulmão
Limite:
Animals
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Reino Unido