Research programmes
Design: Genetic elements
Small circular episomes will be constructed from defined genetic components of human origin. Prototype vectors with defined reporter gene expression cassettes will be used to establish the genetic elements that determine optimal vector performance.
Design: Epigenetic features
Genetic and epigenetic factors regulate gene function in mammalian cells. The rational design of episomal vectors for any long-term application requires a detailed understanding of how epigenetic features, such as changes in chromatin structure, influence gene expression.
Application: Stem cells
Haematopoietic cellsfrom peripheral blood or bone marrow - are effective targets for human gene therapy as they can be removed from the patient treated ex-vivo and then replaced. The possibility of using stem cells to express episomal genes will be evaluated.
Application: Model systems
Episomal vectors will be evaluated for safe, efficient and sustained gene expression in model systems for gene therapy. Vectors will be evaluated for sustained gene transfer to skeletal muscle and liver cells in vitro and in vivo with proteins such as dystrophin, utrophin, apolipoprotein.