Department of Molecular Genetics Thalassemia, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus.
Cyprus School of Molecular Medicine, Nicosia 2371, Cyprus.
Cells. 2021 Jun 14;10(6):1492. doi: 10.3390/cells10061492.
Accessibility of hematopoietic stem cells (HSCs) for the manipulation and repopulation of the blood and immune systems has placed them at the forefront of cell and gene therapy development. Recent advances in genome-editing tools, in particular for clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) and CRISPR/Cas-derived editing systems, have transformed the gene therapy landscape. Their versatility and the ability to edit genomic sequences and facilitate gene disruption, correction or insertion, have broadened the spectrum of potential gene therapy targets and accelerated the development of potential curative therapies for many rare diseases treatable by transplantation or modification of HSCs. Ongoing developments seek to address efficiency and precision of HSC modification, tolerability of treatment and the distribution and affordability of corresponding therapies. Here, we give an overview of recent progress in the field of HSC genome editing as treatment for inherited disorders and summarize the most significant findings from corresponding preclinical and clinical studies. With emphasis on HSC-based therapies, we also discuss technical hurdles that need to be overcome en route to clinical translation of genome editing and indicate advances that may facilitate routine application beyond the most common disorders.
造血干细胞（HSCs）的可及性使其成为细胞和基因治疗发展的前沿，可用于操纵和再生成血液和免疫系统。近年来，基因组编辑工具，特别是簇状规律间隔短回文重复（CRISPR）/CRISPR 相关蛋白（Cas）和 CRISPR/Cas 衍生编辑系统的进步，改变了基因治疗领域。其多功能性和编辑基因组序列以及促进基因缺失、校正或插入的能力，拓宽了潜在基因治疗靶点的范围，并加速了许多可通过移植或修饰 HSCs 治疗的罕见疾病的潜在治愈疗法的发展。正在进行的研究旨在解决 HSC 修饰的效率和精度、治疗的耐受性以及相应疗法的分布和可负担性。在这里，我们概述了 HSC 基因组编辑作为遗传性疾病治疗的最新进展，并总结了相应的临床前和临床研究中的最显著发现。我们重点介绍基于 HSC 的疗法，并讨论在将基因组编辑转化为临床应用过程中需要克服的技术障碍，以及可能促进超越最常见疾病的常规应用的进展。
