A Promising Tool for Gene Therapy
A Promising Tool for Gene Therapy
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发表时间：
2006
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通讯作者：
S. Ghosh;P. Gopinath;A. Ramesh
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作者：
S. Ghosh;P. Gopinath;A. Ramesh
基因治疗是一种很有前途的治疗人类疾病的工具，不能通过合理的治疗方法治愈，其主要成功取决于合适的载体，以提供治疗基因。腺病毒是基因治疗中最常用的载体之一，仅次于逆转录病毒。在过去的十年中，在Ad载体的开发和对与Ad载体系统相关的毒性的理解方面取得了显著进展。Ad载体具有某些优点，例如对不同静止和分裂细胞类型的高转导效率和高水平的短期表达以提供治疗益处。然而，研究人员正面临着与载体的组织特异性靶向和载体介导的免疫原性相关的挑战。本文综述了近年来针对不同的应用，采用不同的方法来改进Ad载体和降低病毒毒性的研究。这些方法包括病毒基因的最小化或消除，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，其导致更安全地使用改善转基因表达持续性的Ad载体系统。此外，肝靶向基因治疗，自杀基因治疗，小干扰RNA的传递，并在临床试验中使用的监管条件下生产重组疫苗的Ad载体的治疗应用进行了讨论。索引号：腺病毒载体;反向末端重复序列;小干扰RNA;科萨基和腺病毒受体。
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 vectors 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. Index Entries: Adenovirus vector; inverted terminal repeat; small interfering RNA; Coxsackie and adenovirus receptor.