中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (29): 4713-4720.doi: 10.3969/j.issn.2095-4344.0631

• 干细胞综述 stem cell review • 上一篇    下一篇

CRISPR/Cas9在造血干细胞移植中的最新研究与进展

杨 慧,朱建伟,路慧丽   

  1. 上海交通大学药学院,细胞工程及抗体药物教育部工程研究中心,上海市 200240
  • 修回日期:2018-05-20 出版日期:2018-10-18 发布日期:2018-10-18
  • 通讯作者: 路慧丽,博士,副研究员,上海交通大学药学院,细胞工程及抗体药物教育部工程研究中心,上海市 200240
  • 作者简介:杨慧,女,1995年生,江苏省盐城市人,汉族,在读硕士,主要从事细胞工程和抗体药物方面的研究。
  • 基金资助:

    国家自然科学基金项目(81273576);上海市科委科技创新行动计划项目(17431904500)

CRISPR/Cas9: research advances in hematopoietic stem cell transplantation

Yang Hui, Zhu Jian-wei, Lu Hui-li   

  1. Engineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
  • Revised:2018-05-20 Online:2018-10-18 Published:2018-10-18
  • Contact: Lu Hui-li, PhD, Associate researcher, Engineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
  • About author:Yang Hui, Master candidate, Engineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81273576; Shanghai Scientific and Technological Innovation Project, No. 17431904500

摘要:

文章快速阅读:

文题释义:
CRISPR/Cas9:
最初在细菌免疫系统里发现,由CRISPR-RNA(crRNA)、转录激活crRNA(tracrRNA)以及Cas9核酸酶组成。crRNA和tracrRNA可被缩短进而整合到一个sgRNA(single guide RNA),引导Cas9酶对目的基因进行特异性识别和剪切。
造血干细胞:具有易于分离、自我更新、分化能力强的特性,使其在临床上具有很大潜力。经过编辑的造血干细胞可以在患有血液、免疫、代谢紊乱等疾病的患者中完成整个造血系统的终身重建。由此,在自体移植和基因治疗方面,具有良好的应用前景。

 

摘要
背景:
CRISPR/Cas9基因编辑系统来源于由成簇规则间隔短回文重复序列(CRISPR)及其相关蛋白(Cas)介导的细菌适应性免疫系统。造血干细胞具有易分离、自我更新分化能力强的优势,已成功应用于恶性血液病、严重的自身免疫性疾病等领域。采用CRISPR/Cas9系统对造血干细胞进行体内、体外编辑,是提高造血干细胞移植治疗水平的研究趋势,在临床上具有很大潜力。
目的:综述CRISPR/Cas9系统在造血干细胞移植领域中的疾病治疗、递送方式、编辑功能优化以及临床应用等方面的最新研究进展。
方法:以“造血干细胞,CRISPR/Cas9,基因编辑,递送;stem cells,CRISPR/Cas9,gene editing,delivery”为关键词,检索CNKI、PubMed数据库、相关临床试验及公司在研产品中2012至2018年的文献,初步筛选后,对保留的61篇文献进行详细研究、归纳和总结。
结果与结论:利用CRISPR/Cas9简易高效的基因编辑能力以及造血干细胞自我更新和分化的能力,编辑过的造血干细胞可以在血液和免疫系统中实现整个造血系统的终身修复重建,在疾病治疗方面具有很大的潜力。CRISPR/Cas9的递送方式目前仍存在局限,需要对其进一步研究和优化,此外,该系统在造血干细胞领域的临床研究及其需应对的伦理和安全问题也需要考虑。

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程
ORCID: 0000-0003-3600-9448(杨慧)

关键词: CRISPR/Cas9, 造血干细胞, 疾病治疗, 递送载体, 临床应用, 国家自然科学基金

Abstract:

BACKGROUND: The CRISPR/Cas9 gene editing system was derived from a bacterial adaptive system mediated by the Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) and CRISPR-associated proteins (Cas). Hematopoietic stem cells (HSCs) are easy to isolate and capable of self-renewal and differentiation into different cell types, and have been successfully applied in the treatment of hematological malignancies and severe autoimmune diseases. In vivo and in vitro HSCs editing using the CRISPR/Cas9 system is a research trend that improves the therapeutic effect of HSCs transplantation, and has great clinical potential.
OBJECTIVE: To review the disease therapeutics, delivery systems, gene editing and clinical application of CRISPR/Cas9 in HSCs transplantation.
METHODS: The key words of “hematopoietic stem cells, CRISPR/Cas9, gene editing, delivery” in Chinese and English were used to search CNKI, PubMed and online databases respectively for relevant articles published from 2012 to 2018. After initial screening, the 61 eligible articles were further analyzed, summarized and concluded.
RESULTS AND CONCLUSION: The simple and efficient gene editing ability of CRISPR/Cas9 can be applied to edit HSCs in vitro and in vivo and assist the clinical achievements of HSCs transplantation, which can reconstitute the life-long repair of hematopoietic system in the blood and immune systems in patients with hematopoiesis deficiencies. The limited delivery vehicles of CRISPR/Cas9 system remain to be further studied and optimized. In addition, the ethical and safety issues of CRISPR/Cas9 system in clinical research of HSCs need to be considered.

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

Key words: Hematopoietic Stem Cells, RNA Editing, Tissue Engineering

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