Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Feb 20, 2015; 5(1): 11-20
Published online Feb 20, 2015. doi: 10.5493/wjem.v5.i1.11
Internal ribosome entry site-based vectors for combined gene therapy
Edith Renaud-Gabardos, Fransky Hantelys, Florent Morfoisse, Xavier Chaufour, Barbara Garmy-Susini, Anne-Catherine Prats
Edith Renaud-Gabardos, Fransky Hantelys, Anne-Catherine Prats, Université de Toulouse, UPS, TRADGENE, EA4554, BP 84225, F-31432 Toulouse, France
Florent Morfoisse, Barbara Garmy-Susini, Inserm, U1048, F-31432 Toulouse, France and Université de Toulouse, UPS, I2MC, F-31432 Toulouse, France
Xavier Chaufour, Centre Hospitalier Universitaire de Toulouse, F-31059 Toulouse and Université de Toulouse, UPS, TRADGENE, EA4554, BP 84225, F-31432 Toulouse, France
Author contributions: Renaud-Gabardos E, Hantelys F, Morfoisse F, Chaufour X, Garmy-Susini B and Prats AC contributed to paper writing.
Conflict-of-interest: The authors declare they have no conflicting interests (including but not limited to commercial, personal, political, intellectual, or religious interests) related to the present work.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Anne-Catherine Prats, PhD, Université de Toulouse, UPS, TRADGENE, EA 4554, I2MC, 1, Avenue Jean Poulhes, BP 84225, 31432 Toulouse cedex 4, F-31432 Toulouse, France.
Telephone: +33-53-1224087 Fax: +33-56-1325622
Received: October 18, 2014
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.

Keywords: Vector, Gene transfer, Internal ribosome entry site, Gene therapy

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.