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首页> 外文期刊>Current gene therapy >Insertional mutagenesis by retroviral vectors: current concepts and methods of analysis.
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Insertional mutagenesis by retroviral vectors: current concepts and methods of analysis.

机译：逆转录病毒载体的插入诱变：当前的概念和分析方法。

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摘要

Retroviral vectors derived from gammaretroviruses or lentiviruses have now been used extensively in clinical gene therapy trials for several diseases including primary immunodeficiencies, beta thalassaemia and adrenoleukodystrophy. Their utility in this setting has been readily demonstrated by the largely favourable outcomes in recent clinical trials, however this success has been marred by the emergence of malignancies in some trials. These malignancies were a consequence of perturbation of cellular proto-oncogene expression by the integrated retroviral vectors, the process of which is referred to as 'insertional mutagenesis' (IM). In this review, the origins of our understanding of IM are reviewed and applied to the clinical gene therapy trials conducted with retroviral vectors. Old and new methods for assessing this phenomenon are discussed with a view to provide a comprehensive account of this emerging field.
机译：衍生自γ逆转录病毒或慢病毒的逆转录病毒载体现已在临床基因治疗试验中广泛用于多种疾病，包括原发性免疫缺陷，β地中海贫血和肾上腺皮质营养不良。在最近的临床试验中，其非常有利的结果已经很容易证明了它们在这种情况下的效用，但是，在某些试验中，由于出现了恶性肿瘤，这种成功已受到损害。这些恶性肿瘤是整合的逆转录病毒载体干扰细胞原癌基因表达的结果，其过程称为“插入诱变”（IM）。在这篇综述中，我们对IM理解的起源进行了综述，并将其应用于使用逆转录病毒载体进行的临床基因治疗试验。讨论了评估这种现象的新旧方法，以期全面介绍这一新兴领域。

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