The main focus of my research is the development of gene and stem cell therapy with the primary aim of developing novel treatments for eye disease. Over the past ten years we have been optimising gene transfer to the eye. We are engaged in a comprehensive programme of work to develop gene therapy for eye disease and in particular for disorders affecting the retina, including inherited retinal degeneration as well as complex diseases such as those associated with retinal and choroidal neovascularisation and posterior uveitis.

My research has utilised a variety of viral vectors, but my main interest is in the development of vector systems based on either adeno-associated virus (AAV) or lentiviruses. We have demonstrated the utility of these systems for gene transfer to the eye. A major aspect of our research is the development and use of a wide variety of genetic and experimental animal models of retinal disorders, including large animal models, in order to assess novel therapeutic approaches. We are engaged in a broad programme of work to demonstrate proof of concept for a number of alternative strategies, including gene replacement therapy and/or delivery of siRNA to treat animal models of inherited retinal degeneration and delivery of genes encoding angiostatic, anti-apoptotic, immunomodulatory or neurotrophic molecules to treat a variety of animal models. We are now also investigating the potential of stem or progenitor cell transplantation to repair degenerating retinae. A recent key discovery is that transplantation of rod precursor cells at a specific stage of development results in their integration and subsequent differentiation into rod photoreceptors that form synaptic connections and improve visual function in mouse models of retinal degeneration. Conversely, transplantation of progenitor or stem cells that are not at this precise ontogentic stage do not show this property and fail to integrate. We are now combining gene therapy approaches with that of stem cell transplantation and using viral vectors carrying genes encoding a variety of transcription factors in order to generate appropriate cells for transplantation from either embryonic or adult-derived stem cells.

In order to deliver new treatments, we have now established a programme of translational research. My research group includes a number of clinicians (clinical training fellows as well as senior clinican/scientists) and we have strong links with a number of biotechnology companies. We have recently established a Department of Health funded clinical trial of gene therapy for a form of severe childhood-onset retinal dystrophy due to mutations in the gene encoding RPE65. This condition is likely to be particularly amenable to effective treatment and the trial should facilitate future trials and underpin the programme of development of treatments for other retinal disorders. The first patients were enrolled in early 2007 and the first results from the trial were published in the New England Journal of Medicine in May 2008.