CRISPR application in hematological disorders: from bench to bedside.

Landmark successes in inherited blood diseases, including sickle cell disease, β-thalassemia, and severe combined immunodeficiency, have demonstrated that precise and durable genetic modifications can be safely and effectively implemented in human hematopoietic cells, positioning hematology at the forefront of translational genome editing.

在遗传性血液疾病中的重大成功，包括镰状细胞性贫血、β-地中海贫血和严重联合免疫缺陷症，已经证明了精确且持久的基因修改可以在人类造血细胞中安全有效地实施，使血液学处于转化基因组编辑的前沿。

Beyond monogenic disease, CRISPR-based approaches are transforming both the biological understanding and treatment of hematologic malignancies by enabling systematic interrogation of cancer dependencies, functional mapping of genetic vulnerabilities, and mechanism-driven target validation, including in vivo and immune-relevant contexts.

除了单基因疾病外，基于CRISPR的方法正在通过系统地探究癌症依赖性、功能映射遗传脆弱性以及包括体内和免疫相关环境下的机制驱动靶点验证，彻底改变血液恶性肿瘤的生物学理解和治疗。

In parallel, therapeutic applications are emerging through the development of engineered cellular therapies, including edited autologous and allogeneic immune effector cells designed to enhance antitumor efficacy, persistence, and immune evasion.

同时，通过开发工程化的细胞疗法，包括编辑的自体和异体免疫效应细胞，旨在增强抗肿瘤效果、持久性和免疫逃逸的治疗应用正在出现。

This review synthesizes recent CRISPR-based advances across benign and malignant hematologic diseases.

本综述综合了近期在良性和恶性血液疾病中基于CRISPR技术的最新进展。

We compare major editing modalities, including nuclease-mediated disruption, base editing, prime editing, and CRISPR-based transcriptional modulation, and highlight key preclinical studies alongside emerging clinical trial data.

我们比较了主要的编辑方式，包括核酸酶介导的破坏、碱基编辑、原位编辑以及基于CRISPR的转录调控，并突出了关键的临床前研究以及新兴的临床试验数据。

We also discuss translational challenges that currently limit broader clinical adoption, including delivery and manufacturing scalability, off-target and genotoxicity risks, tumor and immune heterogeneity, and the long-term durability and fitness of edited cell populations.

我们还讨论了目前限制更广泛临床应用的转化挑战，包括递送和制造的可扩展性、脱靶和基因毒性风险、肿瘤和免疫异质性，以及编辑细胞群体的长期持久性和适应性。

Finally, we outline priorities for the next phase of the field, emphasizing how continued innovation in CRISPR technologies may enable increasingly precise, durable, and mechanism-informed therapeutic strategies in hematology.

最后，我们概述了该领域下一阶段的优先事项，强调了CRISPR技术的持续创新如何可能使血液学中的治疗策略更加精确、持久和机制明确。