Related Experiment Video
Updated: Jul 6, 2026
Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred
Suzanne M K Buckley1, S N Waddington, S Jezzard
1Department of Haematology, Haemophilia Centre and Thrombosis Unit, Royal Free & University College Medical School, London, UK. s.buckley@medsch.ucl.ac.uk
Insights
In utero gene therapy for cystic fibrosis (CF) using adenovirus vectors showed no survival benefit in CF knockout mice. Transient prenatal CFTR expression did not reverse the disease
Area of Science:
- Genetics and Molecular Biology
- Developmental Biology
- Medical Research
Background:
- Cystic Fibrosis (CF) is a severe genetic disorder with early onset, making it a candidate for in utero gene therapy.
- A 1997 study suggested transient prenatal expression of the CF transmembrane conductance regulator (CFTR) via adenovirus could permanently reverse CF pathology in mice.
Purpose of the Study:
- To independently verify the contentious 1997 finding regarding in utero gene therapy for cystic fibrosis.
- To determine if transient prenatal CFTR expression can achieve a lifelong cure for CF intestinal pathology in mice.
Main Methods:
- Utilized an identical adenoviral vector and a genetically inbred CF knockout mouse line (Cftr(tmlCam)).
- Delivered the CFTR-expressing adenovirus to fetal mice.
- Assessed vector DNA and transgenic CFTR expression postpartum and compared survival rates between treated and control groups.
Main Results:
- Vector DNA and transgenic CFTR expression were detected in treated animals post-birth.
- No statistically significant difference in survival was observed between CF knockout mice treated with the CFTR-adenovirus and those treated with a control vector.
Conclusions:
- Transient prenatal expression of CFTR via adenovirus did not lead to a significant improvement in survival for CF knockout mice.
- The findings do not support the hypothesis that temporary in utero gene therapy can permanently reverse cystic fibrosis pathology.
Abstract:
Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero-injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (Cftr(tmlCam)) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr(-/-) mice treated with the CFTR-adenovirus and those treated with the control vector.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
01:24Cystic Fibrosis: Management
Sinus disease and chronic sinusitis...