ArticleGene therapy2004
Widespread and efficient marker gene expression in the airway epithelia of fetal sheep after minimally invasive tracheal application of recombinant adenovirus in utero.
Article in Gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 62 citations in OpenAlex.
- Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.Current stem cell reports · 2019Article
- In Utero Gene Therapy (IUGT) Using GLOBE Lentiviral Vector Phenotypically Corrects the Heterozygous Humanised Mouse Model and Its Progress Can Be Monitored Using MRI Techniques.Scientific reports · 2019Article
- Vector serotype screening for use in ovine perinatal lung gene therapy.Journal of pediatric surgery · 2016Article
- In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application.Molecular therapy. Methods & clinical development · 2016Review
- A novel surgical approach for intratracheal administration of bioactive agents in a fetal mouse model.Journal of visualized experiments : JoVE · 2012Article
- The fetal respiratory system as target for antenatal therapy.Facts, views & vision in ObGyn · 2011Review
- Efficient gene transfer into the mouse lung by fetal intratracheal injection of rAAV2/6.2.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Factors determining the risk of inadvertent retroviral transduction of male germ cells after in utero gene transfer in sheep.Human gene therapy · 2009Article
- Lentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expression.Gene therapy · 2008Article
- Early fetal gene delivery utilizes both central and peripheral mechanisms of tolerance induction.Experimental hematology · 2008Article
- Gene therapy progress and prospects: cystic fibrosis.Gene therapy · 2006Review
- Gene therapy progress and prospects: fetal gene therapy--first proofs of concept--some adverse effects.Gene therapy · 2005Review
- Noninvasive radiological imaging of pulmonary gene transfer and expression using the human sodium iodide symporter.European journal of nuclear medicine and molecular imaging · 2005Article
- Adenovirus-mediated gene therapy enhances parainfluenza virus 3 infection in neonatal lambs.Journal of clinical microbiology · 2004Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic fibrosis is a common lethal genetic disease caused by functional absence of the cystic fibrosis transmembrane conductance regulator (CFTR). Although a candidate disease for in utero gene therapy, demonstration of potentially therapeutic levels of transgene expression in the fetal airways after minimally invasive gene delivery is a mandatory prerequisite before application of this approach in humans can be considered. We report here on the delivery of a beta-galactosidase expressing adenovirus directly to the airways of fetal sheep in utero using ultrasound-guided percutaneous injection of the trachea in the fetal chest. Injection of adenoviral particles to the fetal airways was not associated with mortality and resulted in low-level expression in the peripheral airways. However, complexation of the virus with DEAE dextran, which confers a positive charge to the virus, and pretreatment of the airways with Na-caprate, which opens tight junctions, increased transgene expression, and a combination of these two enhancers resulted in widespread and efficient gene transfer of the fetal trachea and bronchial tree. Using a percutaneous ultrasound-guided injection technique, we have clearly demonstrated proof of principle for substantial transgene delivery to the fetal airways providing levels of gene expression that could be relevant for a therapeutic application of CFTR expressing vectors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.