Gene Therapy for Surfactant Disorders
Lead Research Organisation:
University of Oxford
Department Name: RDM Radcliffe Department of Medicine
Abstract
At birth, some babies fail to breathe due to a failure to inflate their lungs and often this is due to genetic diseases resulting in a lack of surfactant protein. Surfactant forms a thin film that covers the gas exchange surface in the lung. It is required to prevent the lung from collapse. Several proteins are crucial to normal surfactant metabolism, for example, surfactant protein B, surfactant protein C and ABCA3. Absence or reduced function of such proteins due to genetic mutation leads to severe respiratory distress. The outlook for affected babies can be poor and progress in developing treatments has been slow as the majority of such diseases are very rare. In my DPhil project I am investigating gene therapy for surfactant disorders. The principle is to deliver the correct genetic information to specific cells in the lung called alveolar type II cells, the site of surfactant metabolism, using adeno-associated virus (AAV) as a vehicle for delivery. AAV is a non-pathogenic virus which is known for its ability to infect different target tissues with a good safety profile in gene therapy applications. If the delivered genes are expressed long-term in the lung this approach has the potential to treat surfactant disorders. Importantly, even partial correction may have a benefit, for example by extending the window in which lung transplantation could be offered.
People |
ORCID iD |
Stephen Hyde (Primary Supervisor) | |
Helena Meyer-Berg (Student) |
Publications
Meyer-Berg H
(2020)
Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids.
in Stem cell research & therapy
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N013468/1 | 01/10/2016 | 30/09/2025 | |||
1966167 | Studentship | MR/N013468/1 | 01/10/2017 | 30/06/2021 | Helena Meyer-Berg |
Title | Rare is not so rare. |
Description | Blog article on British Society for Gene and Cell Therapy Blog for public outreach and science communication. My aim was to raise awareness for rare diseases. Every single rare disease only affects few people, but overall because there are ca. 8000 of them many people are affected by a rare disease at some point in their lifes. |
Type Of Art | Creative Writing |
Year Produced | 2019 |
Impact | I developed my science communication skills. |
URL | https://www.bsgct.org/rare-not-rare/ |
Description | Gene therapy for lung diseases - Enriching engagement (Public engagement grant) |
Amount | £5,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2019 |
End | 10/2020 |
Description | MRC supplementary funding - exceptional training opportunity |
Amount | £3,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2018 |
End | 10/2020 |
Description | PhD Fellowship |
Amount | € 40,000 (EUR) |
Organisation | German National Academic Foundation |
Sector | Academic/University |
Country | Germany |
Start | 02/2019 |
End | 09/2020 |
Title | RNAscope to measure transgene expression on mRNA level after rAAV delivery |
Description | RNAscope is a commercially available in site hybridisation method. I further developed the method to make it applicable to transgene expression after rAAV vector delivery. |
Type Of Material | Technology assay or reagent |
Year Produced | 2020 |
Provided To Others? | No |
Impact | We plan to publish this method and hope to contribute to more accurate estimates of promoter expression levels for therapeutic transgene delivery. |
Title | SFTPB 121ins genetic modified human embryonic stem cell line |
Description | This human embryonic stem cell line was modified to have the most common mutation in SFTPB (121ins2) causing the fatal genetic condition Surfactant Protein B deficiency. |
Type Of Material | Cell line |
Year Produced | 2020 |
Provided To Others? | No |
Impact | This cell line can be used to grow organoids (3D cell culture models of organs) and has therefore the potential to create a valuable translational model of Surfactant Protein B deficiencies, such as gene therapies and therapeutic gene editing. |
Description | Training partnership for generation of Lung Bud Organoids |
Organisation | Ministry of Science and Innovation (MICINN) |
Department | Institute of Health "Carlos III" (ISCIII) |
Country | Spain |
Sector | Academic/University |
PI Contribution | In a collaboration with ISCIII Madrid, I learnt the crucial steps of lung bud organoids generation. I also conducted studies on rAAV vector tropism in the translational model of the lung parenchyma. We hope to publish this work soon. |
Collaborator Contribution | The collaborators provided lung bud organoids and trained me in their generation. |
Impact | We identified tropisms of rAAV gene therapy vectors in the human lung parenchyma. This was previously unknown and contributes to developing rAAV gene therapies for human lung parenchyma such as surfactant deficiencies. |
Start Year | 2018 |