Our research Current projects Spray on RDEB gene therapy Dr Su Lwin works in London, UK, on gene therapy for recessive dystrophic epidermolysis bullosa (RDEB). People with RDEB have changes in the COL7A1 genes they inherited from both parents so cannot make collagen, an important skin protein. The goal of this work is to develop a way of adding working COL7A1 genes to skin cells taken from each RDEB patient, growing these cells in the laboratory then spraying them onto areas affected by RDEB symptoms. These cells must be shown to survive to make working collagen and functional skin before this can become a realistic therapy and will first be attempted in an animal model. Contents: Project information Abstract Grant Title: Preclinical study of spray-on gene therapy for recessive dystrophic epidermolysis bullosa Investigator: Dr Su Lwin Partner organizations & collaborators: Prof. John McGrath, St. John’s Institute of Dermatology and Dr. Michael Antoniou, Department of Medical and Molecular Genetics, Kings College London, UK. Collaborators Prof. Alain Hovnanian and Dr. Matthias Titeux, INSERM UMR 1163, Imagine Institute, Paris, France. Start Date: 01/06/2019 for 2 years Grant amount: £174,023 Abstract About this research and why it is important: Patient-friendly effective therapies for RDEB are desperately needed. This group proposes to address this challenge by developing a spray-on gene therapy for RDEB designed for longer-lasting therapeutic benefit including prevention of scarring. Recessive dystrophic epidermolysis bullosa (RDEB) is one of the most severe forms of EB with significant disease burden and high mortality due to cutaneous squamous cell carcinoma (cSCC). Resulting from mutations in the COL7A1 gene that produces type VII collagen, it leads to blisters and tissue fragility. Only palliative care is currently available; therefore, patient-friendly effective therapies are an unmet need. This group proposes to address this challenge by developing a spray-on gene therapy for RDEB designed for longer-lasting therapeutic benefit, including the prevention of scarring. Building on the recent gene therapy clinical trial Lenticol-F*, the plan is to supplement RDEB patient's own skin cells with functional copies of the COL7A1 gene. To achieve this, they envisage using a form of disabled virus called lentivirus to deliver the gene into keratinocytes and fibroblasts and then spray them on the affected skin with the aid of the SkinGun™ designed by the biotech company RenovaCare Inc. Initially, the project will seek to generate proof-of-concept and evaluate whether the sprayed cells form functional skin using animal models. Their objective is to assess the efficiency with which these viral vectors deliver the functional gene to patients’ own cells and verify whether the therapeutic benefit is long-lasting. Strategic relevance The reliance on cell spray application to deliver the gene coding for type VII collagen would eliminate the need for invasive procedures and provide a patient-friendly treatment. Moreover, gene supplemented cells could be more quickly grown and stored at low temperatures until the patient is ready to receive them, which would significantly improve the clinical feasibility of gene therapy. Figure 1 illustrates the proposed spray-on gene/cell therapy approach for RDEB. This proposal will allow us to obtain the essential pre-clinical data required for future human applications. In Summary This will allow the researchers to obtain the essential data of spray-on gene therapy required for human applications that can be made more easily available for clinical use, thus benefiting a wider population of individuals with RDEB. *LENTICOL F is funded by Cure EB and administrated by DEBRA UK. To read about the project that has contributed to this new research, please click here. Investigator Biographies Dr Su Lwin Dr Su Lwin is a Dermatology Registrar and an Honorary Clinical Research Fellow at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, and King’s College London. She has been working on EB research as the Lead Clinical Research Fellow on several pioneering gene and cell therapy clinical trials since 2014 when she joined Professor John McGrath’s Lab, including the EBSTEM, GENEGRAFT and LENTICOL-F trials. She continues to collaborate with national and international colleagues to dedicate her research in developing effective and clinically feasible therapies for individuals with EB. John McGrath MD FRCP FMedSci John McGrath holds the Mary Dunhill Chair in Cutaneous Medicine at King’s College London and is Head of the Genetic Skin Disease Unit, as well as Honorary Consultant Dermatologist at St John’s Institute of Dermatology, the Guy’s and St Thomas’ NHS Foundation Trust in London. His main interests are in genetics and regenerative medicine and how these impact on dermatology and skin diseases. He is involved in several next generation sequencing initiatives to improve diagnostics for genodermatoses and is also chief investigator for a number of early phase clinical trials of cell and gene therapies for patients with inherited skin diseases. Dr Michael Antoniou Dr Michael Antoniou is head of the Gene Expression and Therapy Group within the Department of Medical and Molecular Genetics of King’s College London, where he has been based since 1994. His research interests include investigating basic mechanisms of gene regulation and using these discoveries to develop gene-based therapeutic products. With partners in industry Dr Antoniou has developed a highly efficient gene expression platform (UCOE® technology) for the manufacture of therapeutic proteins such as antibodies as well as use in gene therapy medicines. He has also developed a gene therapy medicine that is currently in clinical trials in Italy for the blood disorder b-thalassaemia. In general Dr Antoniou’s group is a leader in developing gene therapy medicines that can function in a highly reproducible and stable manner and thus provide long-term therapeutic efficacy. In this regard, Dr Antoniou’s contribution to this project will be crucial to achieving a lasting therapeutic outcome following gene therapy of RDEB patients.