Development of Gene Therapy and Gene Editing for Lung Disorders: the translation of new gene therapies to the clinic, including the development of new vectors, and evaluation in animal models of disease.

The Gene Medicine Research Group is based in the John Radcliffe Hospital and is focused on the development of new gene therapeutics for lung diesases. We use gene therapy and gene editing approaches employing plasmid, lentiviral and AAV platforms for gene delivery in vivo. We are looking for students interested in the translation of new gene therapies to the clinic, including the development of new vectors, and evaluation in animal models of disease.


More than 7000 diseases have been described with an incidence of less than 1 in 2000 births, such that they are considered to be ‘rare’. The majority of such diseases are genetic and may be amenable to gene therapy. Inherited diseases of the lung such as Surfactant Protein deficiencies result from abnormalities in the formation or composition of surfactant. Some of these disorders cause breathing problems that develop in children and adults, whereas more severe versions present shortly after birth. In the case of Surfactant B deficiency alveolar collapse leads to respiratory distress in neonates, with a poor prognosis and affected babies dying shortly after delivery. Furthermore, due to the lack of donor organs, and the unstable state of the disease, lung transplantation is rarely attempted in such young children. Progress in developing treatments has been slow as the majority of such diseases are ultra rare, with many causative mutations and disparate mechanisms of action. We propose to apply gene therapy and gene editing technologies to repair the mutant genes in lung cells shortly after birth. The full correction of such disorders will be technically very challenging, but we hypothesise that even partial correction may have a significant effect on patient outcome, for example by extending the window in which lung transplantation could be offered.

We have experience of the design, production and utility of two gene delivery technologies for the treatment of lung diseases: viral vectors based on Adeno-Associated Virus (AAV) and Lentivirus (LV) Recombinant AAV is available in a large number of serotypes that we will select to offer efficient targeting of specific lung cell types. We have previously developed a highly potent, Lentiviral vector based on simian immunodeficiency virus to treat cystic fibrosis, where the viral envelope protein has been replaced with the F & HN proteins from Sendai virus. This practice, known as pseudotyping directs highly efficient gene delivery to a range of lung cell types. This project will exploit these lung gene delivery vectors, in combination with cell-specific promoters, to direct long-lasting transgene expression in target cells. The vectors will be evaluated for the potential to reverse disease features in primary human lung cell cultures and mouse models for the treatment of surfactant lung disorders.

This project will be based within the Gene Medicine Group. Students will be exposed to many aspects of the translation of gene therapy research, including vector design and production, and the development of assays for correction of gene defects. In addition to cell and molecular biology, the student will receive training in gene editing, microscopy & in vivo imaging, protein characterisation along with virus production/purification and functional evaluation, PCR, FACS, Western blotting, immunocytochemistry, ELISA, quantitative (RT)-PCR, lentivirus production, & Tangential Flow Filtration (TFF) methods.
As well as the specific training detailed above, students will have access to high-quality training in scientific and generic skills, as well as access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.