PhD thesis of Steevens Bouaziz (Autologous immunotherapy against chronic inflammatory diseases)

Summary

Chronic inflammatory rheumatic diseases (RA) have a significant impact on the lives of affected patients and their families. Etanercept, a biologic targeting TNF-α, has been successfully used for nearly 25 years in RA, but requires weekly administration. Our goal is to create a functional plasmid DNA vector that tackles the existing challenges related to biologics, with the intention of enhancing patient comfort while ensuring effective disease management. We propose that the intramuscular administration of plasmid DNA encoding etanercept may facilitate the autologous production of the drug for an extended period, thus considerably decreasing the need for frequent injections.

In this project, we designed “SpEcTra,” a plasmid DNA construct that meets several key specifications, including muscle-specific expression, production of etanercept as a therapeutic molecule, and the capability to generate DNA minicircles to minimize immunogenic responses. We will validate in 2D and 3D culture mouse and human models.