Internal Ribosome Entry Site-based Vectors for Combined Gene Therapy

Overview

Journal World J Exp Med

Publisher Baishideng Publishing Group

Specialty Biomedical Engineering

Date 2015 Feb 21

PMID 25699230

Citations 24

Authors

Edith Renaud-Gabardos

Fransky Hantelys

Florent Morfoisse

Xavier Chaufour

Barbara Garmy-Susini

Anne-Catherine Prats

Affiliations

Soon will be listed here.

Abstract

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.

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