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Could spray-on gene-modified cells provide a therapeutic treatment for RDEB?

Grant Title: Spray-on gene therapy for recessive dystrophic epidermolysis bullosa: Preclinical studies of lentiviral-mediated COL7A1-supplemented epidermal stem cell and CD39+CD26- fibroblast spray-on therapy

Investigators: Dr Su Lwin, Dr Michael Antoniou and Professor John McGrath

Institution: St. John’s Institute of Dermatology, Department of Medical and Molecular Genetics, Kings College London, UK

Start Date: 01/06/2019 for 2 years

Grant amount:  £174,022.66

Lay Summary

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.

The recent gene therapy clinical trial (Lenticol-F*), conducted by Dr Su Lwin and led by Professor John McGrath, demonstrated that a form of disabled virus, known as a lentivirus is safe in humans and can potentially restore type VII collagen in RDEB. Additionally, the team has noted three therapeutically relevant findings: first, De Luca’s lab showed that skin stem cells from the upper skin layer account for therapeutic longevity of transgenic skin. Second, Watt’s group recently identified a specific fibroblast skin cell population from the lower layer that mediate wound healing and not scarring. Third, spray-on skin cells have been successfully used to treat chronic leg ulcers and burn wounds since 2005. 

The vision for this research is to build on these observations by developing state-of-the-art gene/cell therapy spray consisting of RDEB patient’s own skin cells supplemented with functional copies of COL7A1 gene, thereby ensuring improved therapeutic efficacy and longevity (Figure 1).

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. 

Aims and Objectives

In detail, the group propose to develop a revolutionary spray-on gene therapy for RDEB by using the patient’s own skin cells. The two types of skin cells are keratinocytes (KC) and fibroblasts (FB) which will be supplemented with a functional copy of the COL7A1 (collagen 7)  gene via the use of a disabled viral vector – lentivirus (a safe virus used in gene modification). In the first two years, the team will test: (1) whether the sprayed cells form functional skin using animal models, (2) generate the state-of-the art lentiviral vectors carrying functional copies of COL7A1 (3) isolate the special populations of KC and FB from patients’ skin cells (those identified by De Luca’s Lab and Watt’s Lab as described above) and (4) assess the efficiency with which these viral vectors deliver the functional gene to patients’ own cells. 

These preliminary data will be essential in taking the laboratory experiments to the next stage in the third and fourth years, assessing the safety and wound healing benefits of these state-of-the-art gene-modified RDEB patient cells following delivery using mouse models. 

The use of cell spray application eliminates the need for invasive procedures. Moreover, gene augmented cells are more quickly grown and can be cryopreserved (cells that are cooled below 0 degrees Celsius) which will significantly improve the clinical feasibility of gene therapy. 

RenovaCare Inc, a biotech company has agreed to provide SkinGun™ and expertise to test the gene therapy spray applications for RDEB - a non-commercial agreement for this specific Investigator-led collaboration is currently being drafted between King's College London and RenovaCare Inc.

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 -