University Children's Hospital, Department of Pediatrics I, Hematology and Oncology, University of Tübingen, Germany.
University Children's Hospital, Department of Pediatrics I, Hematology and Oncology, University of Tübingen, Germany.
Blood Rev. 2020 Mar;40:100641. doi: 10.1016/j.blre.2019.100641. Epub 2019 Nov 15.
Due to pioneering in vitro investigations on gene modification, gene engineering platforms have incredibly improved to a safer and more powerful tool for the treatment of multiple blood and immune disorders. Likewise, several clinical trials have been initiated combining autologous hematopoietic stem cell transplantation (auto-HSCT) with gene therapy (GT) tools. As several GT modalities such as lentivirus and gene editing tools have a long developmental path ahead to diminish its negative side effects, it is hard to decide which modality is optimal for treating a specific disease. Gene transfer by lentiviruses is the platform of choice for loss-of-mutation diseases, whereas gene correction/addition or gene disruption by gene editing tools, mainly CRISPR/Cas9, is likely to be more efficient in diseases where tight regulation is needed. Therefore, in this review, we compiled pertinent information about lentiviral gene transfer and CRISPR/Cas9 gene editing, their evolution to a safer platform for HSCT, and their applications on other types of gene disorders based on the etiology of the disease and cell fitness.
由于在基因修饰的体外研究方面的开拓性工作，基因工程平台已经不可思议地改进成为治疗多种血液和免疫疾病的更安全、更强大的工具。同样，已经启动了几项临床试验，将自体造血干细胞移植（auto-HSCT）与基因治疗（GT）工具相结合。由于慢病毒和基因编辑工具等几种 GT 方式还有很长的发展道路要走，才能减少其负面副作用，因此很难确定哪种方式最适合治疗特定疾病。慢病毒基因转移是突变疾病的首选平台，而通过基因编辑工具（主要是 CRISPR/Cas9）进行基因校正/添加或基因破坏，在需要严格调控的疾病中可能更有效。因此，在这篇综述中，我们根据疾病的病因和细胞适应性，编译了有关慢病毒基因转移和 CRISPR/Cas9 基因编辑、它们向更安全的 HSCT 平台的进化以及它们在其他类型基因疾病上的应用的相关信息。
