Vers la thérapie génique non virale

Abstract

In vivo gene transfer might be useful for gene therapy application such as cancer or therapeutic neoangiogenesis. Non-viral gene therapy, which uses plasmid DNA as expression vector, presents several advantages. In particular, plasmids are more simple to develop than viral vectors, and they are not immunogenic. We have improved the safety and efficiency of non viral gene therapy by optimizing plasmid backbone and developing new gene delivery technologies. Backbone optimized minicircles are gene expression vectors of minimal size, which are devoid of bacterial origin of replication and of antibiotic resistance gene. Triple helix affinity chromatography allows rapid obtention of highly purified plasmid preparation, with minimal contamination by endotoxins and bacterial chromosomal linear DNA. Electrotransfer is a physical gene delivery technique with leads to high transgene expression in muscle and tumors after direct intratissular injection. In skeletal muscle, plasmid DNA electrotransfer leads to sustained protein production, for more than 18 months, and the transgene products can be released in the circulation. Preclinical evidence suggests that this technology might be useful for the treatment of hemophilia, beta-thalassemia, rheumatoid arthritis, or metabolic disorders. Finally, chemical DNA delivery vectors might prove useful for the targeting of disseminated metastasis.