Title: Efficient gene transfer into the mouse lung by fetal intratracheal injection of rAAV2/6.2
Authors: Carlon, Marianne *
Toelen, Jaan *
Van der Perren, Anke
Vandenberghe, Luk H
Reumers, Veerle
Sbragia, Lourenço
Gijsbers, Rik
Baekelandt, Veerle
Himmelreich, Uwe
Wilson, James M
Deprest, Jan
Debyser, Zeger # ×
Issue Date: Jul-2010
Publisher: Academic Press
Series Title: Molecular Therapy vol:18 pages:2130-2138
Abstract: Fetal gene therapy is one of the possible new therapeutic strategies for congenital or perinatal diseases with high mortality or morbidity. We developed a novel delivery strategy to inject directly into the fetal mouse trachea. Intratracheal (i.t.) injection at embryonic day 18 (E18) was more efficient in targeting the fetal lung than conventional intra-amniotic (i.a.) delivery. Viral vectors derived from adeno-associated virus serotype 6.2, with tropism for the airway epithelium and not earlier tested in the fetal mouse lung, were injected into the fetal trachea. Bioluminescence (BL) imaging (BLI) was combined with magnetic resonance (MR) imaging (MRI) for noninvasive and accurate localization of transgene expression in vivo. Histological analysis for beta-galactosidase (beta-gal) revealed 17.5% of epithelial cells transduced in the conducting airways and 1.5% in the alveolar cells. Stable gene expression was observed up to 1 month after injection. This study demonstrates that direct injection of rAAV2/6.2 in the fetal mouse trachea is superior to i.a. delivery for transducing the lung. Second, as stable gene transfer was detected up to 1 postnatal month, this approach may be useful to evaluate fetal gene therapy for pulmonary diseases such as cystic fibrosis, requiring both substantial numbers of transduced cells as well as prolonged gene expression to obtain a stable phenotypic effect.
ISSN: 1525-0016
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group for Neurobiology and Gene Therapy
Molecular Virology and Gene Therapy
Basic Research in Gynaecology Section (-)
Biomedical MRI
* (joint) first author
× corresponding author
# (joint) last author

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