Targeting the central nervous system with herpes simplex virus / Sleeping Beauty hybrid amplicon vectors.
Targeting the central nervous system with herpes simplex virus / Sleeping Beauty hybrid amplicon vectors.
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DOI：
10.2174/156652311797415845
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发表时间：
2011-10
影响因子：
3.6
通讯作者：
Bowers WJ
中科院分区：
文献类型：
--
作者：
de Silva S;Bowers WJ
事实证明，对困扰中枢神经系统（CNS）的疾病和病症的可持续治疗对于基于病毒载体的基因治疗领域来说是具有挑战性的。然而，病毒载体技术的最新进展加上高效的递送方法开辟了新的途径，在临床前测试阶段显示出了希望。单纯疱疹病毒/睡美人 (HSV/SB) 混合载体的开发代表了设计针对中枢神经系统的治疗方法的进步，其具有将大的转基因 DNA 片段稳定整合到转导细胞基因组中的潜力。在子宫内将这种混合载体注射到胚胎小鼠大脑中，显示出由于神经元前体细胞群的靶向而具有广泛转基因传播的能力。这种独特的功能提供了在整个大脑中长时间稳定表达转基因的方法，这是治疗进行性中枢神经系统疾病的先决条件。在这篇综述中，我们对 HSV/SB 载体系统的特征以及如何有效地将其用于 CNS 靶向基因治疗策略的推导进行了全面的分析。
The pursuits of sustainable treatments for diseases and disorders that afflict the central nervous system (CNS) have proven challenging for the field of viral vector-based gene therapy. However, recent advances in viral vector technology coupled with efficient delivery methods have opened up new avenues that show promise at the preclinical testing stage. The development of the Herpes Simplex Virus/Sleeping Beauty (HSV/SB) hybrid vector represents such an advance for devising treatments targeting the CNS with its potential for stably integrating large transgenomic segments of DNA within the genomes of transduced cells. In utero administration of this hybrid vector into the embryonic mouse brain has revealed the capacity for widespread transgene dissemination due to the targeting of a neuronal precursor cell population. This unique feature has provided the means to stably express a transgene throughout the brain for prolonged periods, which is a prerequisite for the treatment of progressive CNS disorders. In this review we provide a comprehensive breakdown of the characteristics of the HSV/SB vector system and how it can be efficiently employed in the derivation of CNS-targeted gene therapeutic strategies.