Published online Feb 20, 2015. doi: 10.5493/wjem.v5.i1.11
Peer-review started: October 18, 2014
First decision: November 20, 2014
Revised: December 8, 2014
Accepted: December 18, 2014
Article in press: December 19, 2014
Published online: February 20, 2015
Gene therapy appears as a promising strategy to treat incurable diseases. In particular, combined gene therapy has shown improved therapeutic efficiency. Internal ribosome entry sites (IRESs), RNA elements naturally present in the 5’ untranslated regions of a few mRNAs, constitute a powerful tool to co-express several genes of interest. IRESs are translational enhancers allowing the translational machinery to start protein synthesis by internal initiation. This feature allowed the design of multi-cistronic vectors expressing several genes from a single mRNA. IRESs exhibit tissue specificity, and drive translation in stress conditions when the global cell translation is blocked, which renders them useful for gene transfer in hypoxic conditions occurring in ischemic diseases and cancer. IRES-based viral and non viral vectors have been used successfully in preclinical and clinical assays of combined gene therapy and resulted in therapeutic benefits for various pathologies including cancers, cardiovascular diseases and degenerative diseases.
Core tip: Combined gene therapy has emerged for a few years as a promising strategy to improve treatments of many diseases including cancer, cardiovascular diseases and degenerative diseases. In this context, internal ribosome entry site (IRES)-based vectors provide a powerful system to co-express several therapeutic genes from the same transcription unit. IRESs are translational enhancers, exhibiting tissue-specificity, and activated by stress. Different IRES-based vectors including plasmids, adeno-associated virus-derived and lentiviral vectors have been used successfully in many preclinical protocols of gene therapy. Moreover the few clinical assays launched with IRES-based multicistronic vectors resulted in therapeutic benefits.