中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 2699-2715.doi: 10.4103/NRR.NRR-D-24-01546

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

脑类器官和基因组编辑技术：了解人类大脑发育和疾病的新时代

  

  • 出版日期:2026-07-15 发布日期:2025-10-17

Brain organoids and genome editing: A new era in understanding human brain development and disorders

Min Zhou1, 2, 3, #, Yuanqing Cao4, 5, #, Ke Yue1, 3, #, Wenyu Wu1, 2, 3, Yutong Xie4, 5, Daiyu Hu4, 5, Jingjing Zhao1, 2, 3, Fang Xu5 , Jianrong Guo3 , Zhenzhou Li2, *, Huan Wang3, *, Zhengliang Gao3, 4, 6, *   

  1. 1 Clinical Research Center for Mental Health, Mental Health Center Affiliated to School of Medicine (Shanghai Hongkou Mental Health Center), Shanghai University, Shanghai, China;  2 Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China;  3 Department of Anesthesiology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China;  4 Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China;  5 School of Basic Medicine, Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China;  6 China-Japan Friendship Medical Research Institute, School of Medicine, Shanghai University, Shanghai, China
  • Online:2026-07-15 Published:2025-10-17
  • Contact: Zhengliang Gao, PhD, zhengliang_gao@shu.edu.cn; Huan Wang, PhD, Cheery_Wang@usst.edu.cn; Zhenzhou Li, PhD, lizhenzhou321@163.com.
  • Supported by:
    This work was supported by the Special Project for Clinical Research of Shanghai Municipal Health Commission, No. 202140403 (to HW); Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai, No. PWZxq 2022-05 (to JG); Natural Science Foundation of Ningxia Hui Autonomous Region, No. 2024AAC05084 (to ZL); Ningxia Hui Autonomous Region Key Research and Development Program, No. 2021BEG03084 (to FX); and National Natural Science Foundation of China, Nos. 32370895 and 32070862 (both to ZG).

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摘要：

脑类器官是体外培养的人工神经组织，包含多种细胞类型以及结构和/或功能脑区。脑类器官可部分模仿大脑的生理活动和患病过程。由于其可操作性和样品可及性，脑类器官在体外单层细胞培养模型和体内动物模型之间起着桥梁的作用。过去10年间，随着研究的不断深入，越来越多的脑类器官诱导方法应运而生，但是如何确保脑类器官的复杂性与稳定性，将成为未来研究的核心课题。CRISPR/Cas9基因组编辑和谱系追踪系统等强大技术的整合将促进脑类器官的广泛应用。此次综述讨论了脑类器官的产生和应用以及其在神经发育、疾病建模和机制研究中与基因组编辑技术的整合。文章指出将脑类器官和基因组编辑技术的创新结合可为探索人类神经系统和相关疾病研究提供了新的视角。

https://orcid.org/0000-0001-5788-4095 (Zhengliang Gao)

关键词: 脑疾病, 脑类器官, CRISPR/Cas9, 疾病建模, 药物筛选, 基因组编辑, 人脑发育, 谱系追踪, 类器官建模, 干细胞分化

Abstract: Brain organoids are artificial neural tissues derived in vitro, containing a variety of cell types, as well as structural and/or functional brain regions. They can partially mimic brain physiological activities and diseased processes. Owing to their operability and sample accessibility, brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models. An increasing number of induction protocols for brain organoids have been developed over the preceding decade. A key future research direction will focus on ensuring the complexity and quality of brain organoids. The integration of powerful technologies, such as the CRISPR/Cas9 genome editing and lineage tracing systems, shall precipitate practical and broad applications of brain organoids. In this review, we discuss the generation and application of brain organoids, as well as their integration with genome editing technologies, in the study of neural development, disease modeling, and mechanistic investigations. The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.

Key words: brain disorder, brain organoid, CRISPR/Cas9, disease modeling, drug screening, genome editing, human brain development, lineage tracing, organoid modeling, stem cell differentiation