With the advent of safer and more efficient gene transfer methods, gene therapy has become a viable solution for many inherited and acquired disorders. Hematopoietic stem cells (HSCs) are a prime cell compartment for gene therapy aimed at correcting blood-based disorders, as well as those amenable to metabolic outcomes that can effect cross-correction. While some resounding clinical successes have recently been demonstrated, ample room remains to increase the therapeutic output from HSC-directed gene therapy. In vivo amplification of therapeutic cells is one avenue to achieve enhanced gene product delivery. To date, attempts have been made to provide HSCs with resistance to cytotoxic drugs, to include drug-inducible growth modules specific to HSCs, and to increase the engraftment potential of transduced HSCs. This review aims to summarize amplification strategies that have been developed and tested and to discuss their advantages along with barriers faced towards their clinical adaptation. In addition, next-generation strategies to circumvent current limitations of specific amplification schemas are discussed.

中文翻译：

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走向体内扩增：克服在移植和基因治疗中使用造血干细胞的障碍。

随着更安全，更有效的基因转移方法的出现，基因治疗已成为许多遗传性和后天性疾病的可行解决方案。造血干细胞（HSC）是基因治疗的主要细胞区室，旨在纠正基于血液的疾病以及那些可能影响交叉校正的代谢结果的疾病。尽管最近已经证明了一些巨大的临床成功，但是仍有足够的空间来增加HSC指导的基因治疗的治疗效果。治疗性细胞的体内扩增是获得增强的基因产物递送的途径之一。迄今为止，已经尝试向HSC提供对细胞毒性药物的抗性，包括HSC特异的药物诱导的生长模块，并增加转导的HSC的植入潜能。这篇综述旨在总结已经开发和测试的扩增策略，并讨论其优势以及其临床适应性面临的障碍。此外，讨论了避免特定扩增方案当前局限性的下一代策略。