中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (9): 1463-1469.doi: 10.3969/j.issn.2095-4344.2017.09.027

• 干细胞综述 stem cell review • 上一篇    下一篇

基因修复β-地中海贫血患者诱导多能干细胞可否成为治疗的希望?

李玲丽,张风波,李  崎,马燕琳   

  1. 海南医学院附属医院海南省人类生殖与遗传重点实验室/生殖医学科,海南省海口市  570102
  • 出版日期:2017-03-28 发布日期:2017-03-31
  • 通讯作者: 马燕琳,博士,教授,海南医学院附属医院海南省人类生殖与遗传重点实验室/生殖医学科,海南省海口市 570102
  • 作者简介:李玲丽,女,1989年生,湖南省益阳市人,汉族,海南医学院在读硕士,主要从事生殖与遗传研究。
  • 基金资助:

    国家国际合作重大专项课题 (2014DFA30180);海南省普通高等学校研究生创新科研课题立项(Hys2016-8)

Gene therapy with induced pluripotent stem cells: a hope for beta thalassemia?

Li Ling-li, Zhang Feng-bo, Li Qi, Ma Yan-lin   

  1. Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research/Department of Reproductive Medicine, the Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
  • Online:2017-03-28 Published:2017-03-31
  • Contact: Ma Yan-lin, M.D., Professor, Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research/ Department of Reproductive Medicine, the Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
  • About author:Li Ling-li, Studying for master’s degree, Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research/Department of Reproductive Medicine, the Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
  • Supported by:

    the National International Cooperation Project of China, No. 2014DFA30180; the Innovative Subjects of Postgraduates in Colleges and Universities in Hainan Province, No. Hys2016-8

摘要:

文章快速阅读:

文题释义:
β-地中海贫血:
为单基因疾病,由于位于Ⅱ号染色体上的β珠蛋白基因突变,导致正常β珠蛋白肽链缺失或合成量不足,α肽链相对过剩并沉积在红细胞膜上,使红细胞破坏出现溶血性贫血。
CRISPR/Cas9:是细菌和古细菌在长期演化过程中形成的一种适应性免疫防御,可用来对抗入侵的病毒及外源DNA。CRISPR/Cas9 系统通过将入侵噬菌体和质粒DNA的片段整合到CRISPR中,并利用相应的 CRISPR RNAs(crRNAs)来指导同源序列的降解,从而提供免疫性。

 

摘要
背景:
对于重型β-地中海贫血,目前惟一的根治方法就是造血干细胞移植,但由于合适供者来源受限及费用昂贵,大部分患者难以得到救治。体细胞重编程技术如今已日臻成熟,在患者诱导多能干细胞中进行基因修复成为了β-地中海贫血治疗的希望。
目的:通过论述ZFNs、TALENs、CRISPR/Cas 3种基因编辑技术体现CRISPR/Cas的优势,以及论述基因编辑技术在动物模型疾病治疗中的初步实验结果,从而展望基因编辑技术对β-地中海贫血进行基因治疗并且应用于临床的可能性。
方法:以“beta thalassemia,genetic therapy,genome editing,homologous recombination,iPSCs”为英文检索词,以“β-地中海贫血,诱导多能干细胞”为中文检索词,由第一作者检索 1989至2015年PubMed数据库、中国期刊全文数据库,查阅近年β-地中海贫血的发生率和分布情况以及β-地中海贫血基因治疗的相关文献,最终保留67篇文献。
结果与结论:随着基因编辑技术的发展,出现了3种定向基因编辑技术,包括ZFNs、TALENs、CRISPR/Cas技术。以地中海贫血患者来源的诱导多能干细胞为靶细胞,通过ZFNs、TALENs及CRISPR/Cas9技术对疾病基因进行纠正,完成对致病基因的治疗。CRISPR/Cas系统相对于其他基因编辑技术更加简单快捷、安全高效,应用也更加广泛,利用CRISPR/Cas9系统修复β-地中海贫血患者诱导多能干细胞、生殖细胞、受精卵、胚胎中β珠蛋白基因,将为今后临床的应用奠定基础。

 

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: 0000-0003-4743-3578(李玲丽)

关键词: 干细胞, 移植, 基因治疗, β-地中海贫血, CRISPR/Cas9, 诱导多能干细胞

Abstract:

BACKGROUND: Beta thalassaemia is a monogenic disease, which lacks effective clinical treatments. Hematopoietic stem cell transplantation currently is the only radical treatment for beta thalassaemia, but the limits of suitable donor and costs minimize its clinical application. Given the technology of reprogramming using somatic cells is well established, gene therapy using induced pluripotent stem cells has become the new direction of beta thalassaemia treatment.
OBJECTIVE: To put forward the advantages of CRISPR/Cas9 technology in gene therapy of beta thalassaemia in the future by summarizing the mechanisms of three kinds of gene editing technologies and the preliminary experimental results in animal models.
METHODS: In order to search relevant articles about beta thalassaemia, the first author retrieved PubMed database and CNKI (from 1989 to 2015) using the key words of “beta thalassemia, genetic therapy, genome editing, homologous recombination, iPSCs” in English and Chinese, respectively. After eliminating literatures which were irrelevant to research purpose or containing a similar content, 67 articles were chosen for further analysis.
RESULTS AND CONCLUSION: Gene editing technology has made considerable progress and three kinds of directed gene editing technologies have been developed, including ZFNs, TALENs, CRISPR/Cas technology. By targeting induced pluripotent stem cells from thalassemi patients, these three kinds of gene editing technologies have been expected to correct pathogenic genes of thalassemia. The CRISPR/Cas system is more simple, rapid, safe and efficient than the others. The CRISPR/Cas9 system is expected to repair β-globin genes in the induced pluripotent stem cells, germ cells, fertilized eggs and embryos from beta thalassaemia patients, laying the foundation for future clinical application.

 

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: beta-Thalassemia, Induced Pluripotent Stem Cells, Targeted Gene Repair, Tissue Engineering

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