Gutless adenovirus: last-generation adenovirus for gene therapy
Gutless adenovirus: last-generation adenovirus for gene therapy
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DOI：
10.1038/sj.gt.3302612
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发表时间：
2005-10-01
期刊：
影响因子：
5.1
通讯作者：
Chillon, M
中科院分区：
文献类型：
--
作者：
Alba, R;Bosch, A;Chillon, M
由于与第一代和第二代腺病毒载体相比，相关的体内免疫反应大大降低，同时保持了较高的转导效率和向性，因此上一代腺病毒载体，也称为依赖帮助者或无内脏腺病毒，对基因治疗非常有吸引力。如今，无肠腺病毒被施用于不同的器官，如肝脏、肌肉或中枢神经系统，在啮齿动物和灵长类动物中实现了高水平和长期的转基因表达。然而，由于缺乏所有的病毒编码区，无胆载体需要由辅助病毒提供反式病毒蛋白。为了从最终的制剂中去除辅助病毒的污染，已经产生了基于去除辅助包装信号的不同系统，其中以Cre-loxP系统使用最多，但污染水平仍高达0.1-1%，无法用于临床试验。最近制定的策略，以避免/减少帮工污染进行了审查。
Last-generation adenovirus vectors, also called helper-dependent or gutless adenovirus, are very attractive for gene therapy because the associated in vivo immune response is highly reduced compared to first- and second-generation adenovirus vectors, while maintaining high transduction efficiency and tropism. Nowadays, gutless adenovirus is administered in different organs, such as the liver, muscle or the central nervous system achieving high-level and long-term transgene expression in rodents and primates. However, as devoid of all viral coding regions, gutless vectors require viral proteins supplied in trans by a helper virus. To remove contamination by a helper virus from the final preparation, different systems based on the excision of the helper-packaging signal have been generated Among them, Cre-loxP system is mostly used, although contamination levels still are 0.1-1% too high to be used in clinical trials. Recently developed strategies to avoid/reduce helper contamination were reviewed.