摘要
基因治疗作为一种新的疾病治疗手段,为传统医药无法治愈的疾病的治疗带来了新的希望。它主要通过使用载体等其他递送系统将外源基因导入体细胞内,或使用基因编辑技术直接实现基因的碱基替换、敲入或敲除,或将某一组织器官的细胞在体外经基因编辑技术修饰或改造后重新回输至体内,以修复受损基因,纠正基因功能,最终达到治疗疾病的目的。目前,基因编辑技术与细胞治疗相结合的基因治疗方法已在多种疾病中实现了临床实验,例如血友病、镰刀细胞贫血、免疫系统缺陷疾病等,且随着基因编辑技术以及干细胞技术的出现,基因治疗有了新的革新和突破,但两者相结合潜在的弊端也同样制约着基因治疗的发展,比如脱靶效率、载体的导入效率、PAM(protospacer adjacent motif)序列的制约和对P53基因的影响等。随着技术的进一步革新和发展,基因治疗的方法、技术以及理论逐渐完善,未来基因治疗将有可能为更多遗传性疾病甚至复杂性疾病的治疗提供新思路。本文就基因治疗的方法和发展前景进行了概述,以期为基因治疗未来研究工作的开展提供参考。
As a new method of disease treatment,gene therapy brings new hope for the treatment of diseases that cannot be cured by traditional medicine.It can repair damaged genes,correct gene function,and finally achieve the purpose of treating diseases by introducing exogenous genes into somatic cells by using delivery system such as vector,or directly realizing gene base substitution,knock in or knock out by using gene editing technology,or cells of a certain tissue and organ re-injecting into the body after being modified by gene editing technology in vitro.At present,gene therapy combining gene editing technology with cell therapy has been clinically applied in various diseases,such as hemophilia,sickle cell anemia and diseases of immune system deficiency.With the emergence of gene editing technology and the development of stem cell technology,gene therapy will usher in new innovations and breakthroughs.However,the potential drawbacks of their combination also restrict the development of gene therapy,such as the efficiency of targeting and vector introduction,the restriction of PAM sequence and the influence on p53 gene.With further innovation and development of technology,the method,technology and theory of gene therapy are gradually improved.In the future,gene therapy may provide new ideas for the treatment of more genetic diseases and even complex diseases.In this paper,the methods and development prospects of gene therapy are discussed in order to provide reference for the future research of gene therapy.
作者
杨鑫宇
王大勇
高旭
YANG Xin-Yu;WANG Da-Yong;GAO Xu(Department of Biochemistry and Molecular Biology,Harbin Medical University,Harbin 150081,China;Translational Medicine Research and Cooperation Center of Northern China,Harbin Medical University,Harbin 150081,China;Heilongjiang Academy of Medical Sciences,Harbin 150081,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2020年第11期1265-1272,共8页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金(No.81701078和No.81773165)
黑龙江省自然科学基金(No.QC2017090)
黑龙江省普通本科高等学校青年创新人才培养计划(No.UNPYSCT-2016190)
中国博士后科学基金(面上资助)(No.2016M600261)
中国博士后科学基金(特别资助)(No.2018T110317)
哈尔滨医科大学校创新科学研究资助项目(No.2016JCZX37)
黑龙江省博士后资助经费(No.LBH-Z15163)。
关键词
基因治疗
CRISPR/Cas9
细胞疗法
基因编辑
gene therapy
CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/CRISPR associated nuclease 9)
cell therapy
gene editing
