Application: Model systems
Key objectives
The objective of this section is to exploit the expression systems developed on the basis of experiments developed to design safe, efficient and sustained gene expression in model systems for gene therapy. Specifically, the use of these episomal vectors developed within EPI-vector will be evaluated for use in the genetic therapy of neuromuscular, cardiovascular and liver specific diseases. Episomal vectors will be evaluated for sustained gene transfer to skeletal muscle and liver cellsin vitroandin vivo. These vectors will be engineered to encode proteins such as dystrophin, utrophin, apolipoprotein-E. The key objectives of this study will be to define:
- The use of extra-chromosomal gene delivery systems to delivery therapeutic gene expression in model systems for human disease. These studies will define long-term clinical potential of episomal gene delivery vectors for gene therapy.
- A detailed profile of episome function to delivery efficient, sustained and tissue specific gene expression. Cell culture and animal models for gene therapy in liver will be developed to benchmark behavior of the prototype vectors as a means of defining improved performance of vectors developed within EPI-vector.
Functionality of prototype episomal vectors and refined vectors developed within EPI-vector will be evaluated at the levels of cell retention and cellular heritability, transgene expression,in vivodelivery and therapeutic efficacy.
Deliverables
The part of the project will provide validation and optimization ofin vivoprotocols for episomal vector delivery to skeletal muscle and liver cells. Skeletal muscle and liver represent organs of major importance for therapeutic applications that are either in clinical trial or preclinical development. Therapeutic episomal vectors carrying therapeutic genes will be used to evaluate the prospect of correcting common genetic defects in muscle and liver specific diseases.