Episomal vectors as gene delivery systems for therapeutic application

Final Report Summary - EPI-VECTOR (Episomal vectors as gene delivery systems for therapeutic application)

Many chronic human diseases cause great suffering as a result of inherited and sporadic genetic mutations. In many cases, gene therapy is able to provide therapeutic benefit if the gene defect can be complemented by expression of a normal gene product in the affected cells. Protocols have been developed for this purpose. However, systems that are currently being evaluated in clinical trials suffer from potential deficiencies that compromise safety. EPI-VECTOR aimed to develop extra-chromosomal gene delivery systems for gene therapy and evaluate protocols for their safe use in preclinical model systems.

The genetic elements that regulate chromatin function at natural chromosomal loci and the molecular mechanisms that regulate function are known. Even so, it has proved an immense challenge to understand how these genetic elements might be configured to provide regulated, efficient and sustained gene expression from extra-chromosomal DNA. Experience of the best extra-chromosomal gene expression systems currently available was used to develop a new generation of DNA vectors for safe and efficient therapeutic application.

A really big problem in performing gene therapy is that the correcting gene is often copied into protein rather inefficiently in the target cells. More worryingly, the expression is commonly maintained for only a short time. Scientists have developed vector systems to overcome this the lentivirus system that was used by the French and North American groups to treat SCID kids actually maintains expression by becoming a fixed part of the genetic material technically speaking, the vector is said to integrate into the cells' chromosomes. Yet, while this gives a good result in terms of treating the condition, the side effects of integration can potentially lead to cancer.

EPI-VECTOR set out to design gene therapy systems that are efficient but more importantly safe. Unlike the major systems that are being used at present, our system used only components of human origin. This will prevent any complications from using DNA or proteins from viruses. Also, our system will not disrupt the host chromosomes, but instead provide a vector that mimics their behaviour.

Final Report Summary - EPI-VECTOR (Episomal vectors as gene delivery systems for therapeutic application)

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