Considerable effort has been devoted to the development of gene delivery strategies for the treatment of inherited and aquired disorders in humans. Ex vivo gene therapies are based on removing cells from a patient, introducing a therapeutic gene construct into the cells, and implanting the engineered cells back into the patient. Currently, both viral and non-viral methods are used for gene delivery. Viral vectors are efficient in gene transfer, but their use raises serious safety concerns. Non-viral methods are usually safer but less efficient in providing long-term therapeutic transgene expression. Transposable elements can be considered as natural, non-viral delivery vehicles capable of efficient genomic insertion. In this project, novel gene transfer technologies will be established by developing transposon vectors that mediate efficient and targeted integration of therapeutic genes into the genome. Therapeutic gene constructs will be made in transposon vectors, and delivered into cells ex vivo, using cutting edge non-viral nucleic acid delivery methods. Application of reversible implantation systems (collagen implants, skin biopumps, and encapsulated cells) will be explored. Animal disease models will include copper metabolism diseases, anemia, hypercholesterolemia, bleeding disorders, chronic grnulomatous disease and neurological disorders. Genomic insertion, transgene expression and phenotypic correction will be investigated. Safety issues of transposon vector administration and genomic integration will be addressed. The involvement of three SMEs will mobilise industrial know-how and technology. This project will develop, test and apply new therapeutic tools for somatic gene therapy as an alternative to currently used viral and non-viral technologies, and will have the potential to offer new solutions for diseases that impose significant impairment to citizens¿ quality of life, as well as burdens on health care services in Europe
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