Renaud-Gabardos Edith, Hantelys Fransky, Morfoisse Florent, Chaufour Xavier, Garmy-Susini Barbara, Prats Anne-Catherine
Edith Renaud-Gabardos, Fransky Hantelys, Anne-Catherine Prats, Université de Toulouse, UPS, TRADGENE, EA4554, BP 84225, F-31432 Toulouse, France.
World J Exp Med. 2015 Feb 20;5(1):11-20. doi: 10.5493/wjem.v5.i1.11.
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.
基因治疗似乎是一种治疗不治之症的有前景的策略。特别是，联合基因治疗已显示出提高的治疗效率。内部核糖体进入位点（IRESs）是天然存在于少数mRNA的5'非翻译区的RNA元件，是共表达多个感兴趣基因的有力工具。IRESs是翻译增强子，允许翻译机制通过内部起始来启动蛋白质合成。这一特性使得设计出从单个mRNA表达多个基因的多顺反子载体成为可能。IRESs表现出组织特异性，并在整体细胞翻译受阻的应激条件下驱动翻译，这使得它们在缺血性疾病和癌症中出现的缺氧条件下进行基因转移时很有用。基于IRES的病毒和非病毒载体已成功用于联合基因治疗的临床前和临床试验，并对包括癌症、心血管疾病和退行性疾病在内的各种病症产生了治疗效果。
