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Expression of genes of biotechnological interest in mammalian cells

This project aims to identify epigenetic regulatory sequences that may mediate more predictable, higher and/or more stable expression of transgenes in mammalian cells, and to identify more effective gene transfer techniques. This work has led to the development of new methods that were successfully applied to the synthesis of therapeutic proteins, and they may improve the development of new approaches to treat muscular dystrophies by cell therapy.

Stable and efficient production of heterologous proteins in mammalian cells and transgenic organisms is limited by technological bottlenecks. For instance, the establishment of stable cell lines requires the production and analysis of numerous clonal cell lines in order to detect the most efficient producer cells. Our work indicates that potent epigenetic insulator elements can be identified from genomes and enhance and stabilize a very high expression of therapeutic proteins by cultured cells. These discoveries led to the creation of biotechnology companies, such Selexis SA in Switzerland and Selexis Inc. in the U.S., which have become world leaders in the manufacture of cells producing recombinant therapeutic proteins.

These genetic elements also allow the expression of transgenes in animal models of incurable human diseases. Our work has shown an improvement in the expression of therapeutic proteins, and therefore therapeutic efficacy in treatment models for Duchenne muscular dystrophy by gene therapy. Favorable results were also obtained from the use of adult stem cells that may be used in cell therapies. By this work, we hope to reach effective therapies for these diseases.

 

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Colony of CHO cells stably expressions a green fluorescent protein (GFP). the expression vector used in this study allows to obtain homogenous colonies which highly express the transgene.


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