Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Many diseases, including cancer, heart disease and diabetes, are caused by the body's cells and tissues malfunctioning. The behaviour of any cell is 'programmed' by its genes and researchers have found that cell behaviour can be altered by changing DNA, RNA and other genetic material in the cell. Gene therapies work by inserting new genetic material into malfunctioning cells, and 'reprogramming' them to function more normally, or by inserting genetic material into a normal cell to produce a new protein (e.g. for a vaccine). Gene therapy offers hope to patients with diseases that have been, up to now, incurable. The UK has excellent teams of researchers who are exploring this exciting topic. Unfortunately, some of the essential materials for gene research are in short supply in the UK, as are skilled technicians to work on the research. There is a particular shortage of viral vectors - special viruses that can be 'loaded' with genetic material and inserted into malfunctioning cells, where their 'payload' replaces genes causing the malfunction. The UK's scientists are held back by these shortages and forced to rely on overseas suppliers; or research is delayed due to difficulties in recruiting staff. This leads to delays in the discovery of new treatments for desperately ill patients. Another important challenge for UK researchers is that achieving great results in the lab is only half the story - before a new treatment can be offered to patients, it must be approved: shown to be safe, effective and affordable. These new treatments are great opportunities for new companies, new jobs and for the UK economy, so academics need support in patenting their discoveries, in undertaking clinical trials and in setting up companies to make new therapies. The MRC and LifeArc have recognised these important issues and are funding a network of hubs around the UK to generate the vital components for gene therapies and to train the skilled personnel needed. The NHSBT Innovation Hub for Gene Therapies will link with the other new hubs around the UK to address these needs. We will work with academic teams to produce the gene therapy components needed, we will train technicians and scientists in producing these at the quality needed for use in clinical trials, and we will support academics in taking their results from the lab to the hospital and the market. Our plan is as follows: 1. To agree our role in the network with the other hubs, MRC, LifeArc and Cell and Gene Therapy Catapult (C>C). We are particularly well placed for flexible viral vector production, quality control and training, and we expect to contribute this to the network, while also collaborating with C>C on production, with LifeArc on commercialisation and patenting, and with other hubs, as requested by the network coordinators.. 2. To install a new viral vector production platform, already selected by C>C as being particularly suitable to meet the needs of UK academic teams. We'll then work with the C>C to ensure it's certified for quality assurance (and so ready to produce clinical grade components). This new platform will produce a specific type of viral vector - adeno-associated-viral vectors (AAVs); this will complement our other platform, producing lentiviral vectors, as well as our existing platform for plasmids (another important gene therapy ingredient). 3. To be assigned academic clients and their projects by the coordinating committee, and then to work with these teams to put in place a production line and training programme that meets their needs. A flexible and customised approach is important, as every academic project will be different. 4. To build a reputation and customer base that makes the NHSBT Hub a 'go to' destination for viral vector services. As a not-for-profit NHS organisation, our aim is to be sustainable, provide excellent value for the benefit of the UK gene therapy community and, ultimately, to save and improve more lives.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Background The conjunctiva is a thin membrane that covers and protects the surface of the eye. It lines the inner surfaces of the upper and lower eyelids creating anatomical spaces between the eyelids and eyeball known as conjunctival fornices. The conjunctiva may become irreversibly damaged and the fornices obliterated by scarring following injuries such as chemical burns, severe infections or autoimmune disease. When severe, this prevents eyelid closure, restricts movement and causes lid deformity leading to painful blindness when the cornea (optically clear structure on the eye's surface) becomes opaque due to progressive abrasion and scarring. Such patients comprise up to ten percent of patients attending specialist ocular surface clinics. So far techniques to replace conjunctiva have failed as a result of recurrent scarring or because the graft has been insufficient in size. These patients invariably suffer visual loss due to corneal disease which cannot be addressed with clear corneal grafts unless the ocular surface is restored first. I will develop a novel biological and synthetic material on which the patient's own conjunctival cells will be cultivated to create larger grafts for transplantation. Conjunctiva will be retrieved from a cadaver and the cellular (living components) removed leaving behind a 'biological scaffold'. Eventually this research will lead to a patient's own cells being seeded on the developed substrate and the resulting graft transplanted into the same individuals so that an immune reaction should not occur. Examples of biological scaffolds successfully transplanted in humans include skin, heart valves and trachea. The synthetic substrate will be developed on a well tolerated biomaterial (ePTFE), commonly known as 'Gore-Tex', also used in medical devices such as grafts for blood vessel repair. This has been previously shown to support fornix reconstruction but growth of conjunctiva on its surface would be novel. I plan to render the surface conducive to cell growth by incorporating chemical groups and proteins on the ePTFE surface. My preliminary work has shown conjunctival growth on gas plasma treated ePTFE but further development is required to achieve optimal results. Aim: To develop decellularised human conjunctiva and ePTFE with novel surface chemistry to enable conjunctival expansion for future use as grafts. How research will be conducted Human conjunctival tissue will be obtained from deceased patients at the Royal Liverpool University Hospital and the research carried out in laboratories in the University of Liverpool. A novel protocol for the decellularisation of conjunctiva will be developed through collaboration with NHS Blood and Transplant, Liverpool. The ePTFE will undergo chemical modification by a process that changes surface chemistry (gas plasma treatment) and binding of proteins. Once both substrates have been developed, cadaveric conjunctival biopsies will be cultured on the two novel surfaces leading to the production of two conjunctival constructs. The physical and biological properties of the engineered constructs will be tested and compared to natural human conjunctiva. Expected outcomes This research will benefit patients who require conjunctival replacement for reasons including glaucoma surgery, excision of conjunctival growths and fornix reconstruction. The greatest impact of this research will be in patients with severe ocular surface disease ranging from autoimmune conditions such as mucous membrane pemphigoid to those with chemical burns. These novel grafts will enable ophthalmologists to develop new surgical strategies to reconstruct the surface of the eye. This will profoundly reduce pain and improve visual outcomes for patients with severe conjunctival disease. The novel materials developed through this fellowship could also lead to cell replacement therapies to treat other incurable eye diseases in the future.