Adenoviral vectors - A promising tool for gene therapy
Adenoviral vectors - A promising tool for gene therapy
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DOI：
10.1385/abab:133:1:9
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发表时间：
2006-04-01
影响因子：
3
通讯作者：
Ramesh, A
中科院分区：
文献类型：
--
作者：
Ghosh, SS;Gopinath, P;Ramesh, A
基因治疗是治疗无法通过合理治疗治愈的人类疾病的一种有前景的工具，其主要成功取决于合适的载体来传递治疗基因。腺病毒（Ads）是基因治疗中最常用的载体之一，仅次于逆转录病毒。在过去十年中，在Ad载体的开发和对Ad载体系统毒性的理解方面取得了显著进展。Ad载体对不同的静止和分裂细胞类型具有较高的转导效率和高水平的短期表达，从而提供治疗效果。然而，研究人员正面临着与组织特异性靶向载体和载体介导的免疫原性相关的挑战。本文主要综述了在不同的应用中采用改进Ad载体和降低病毒毒性的方法的研究。这些方法包括最小化或消除病毒基因，将载体重新靶向感兴趣的组织，以及产生免疫受损的重组载体，从而更安全地使用Ad载体系统，从而提高转基因表达的持久性。此外，还讨论了Ad载体在肝脏靶向基因治疗、自杀基因治疗、小干扰RNA递送和在临床试验中使用的调节条件下生产重组疫苗方面的治疗应用。
Gene therapy is a promising tool for treatment of the human diseases that cannot be cured by rational therapies, and its primary success depends on suitable vectors to deliver therapeutic genes. Adenoviruses (Ads) are among the most commonly used vectors for gene therapy, second only to retroviruses. During the last decade, remarkable progress has been made in the development of Ad vectors and in the understanding of the toxicity related to the Ad vector system. Ad vector has certain advantages such as high transduction efficiency for different quiescent and dividing cell types and high levels of short-term expression to provide therapeutic benefits. However, researchers are facing the challenges associated with tissue-specific targeting of vector's and the vector-mediated immunogenicity. This review mainly focuses on the studies that have employed methods to improve Ad vectors and reduce viral toxicity for different applications. These methods include minimization or elimination of viral genes, retargeting of vector to the tissue of interest, and generation of immunocompromised recombinant vectors that lead to safer use of Ad vector systems that improve persistence of transgene expression. Moreover, the therapeutic applications of Ad vectors for liver-targeted gene therapy, suicide gene therapy, delivery of small interfering RNA, and production of recombinant vaccine under regulated conditions used in clinical trials are discussed.