Synthetic Biology Journal ›› 2023, Vol. 4 ›› Issue (4): 703-719.DOI: 10.12211/2096-8280.2022-054

• Invited Review • Previous Articles     Next Articles

Application and prospect of CRISPR-Cas9 system in tumor biology

Mengdan MA1,2,3, Mengyu SHANG1,2,4, Yuchen LIU1,2   

  1. 1.The first Affiliated Hospital of Shenzhen University,Shenzhen Second People′s Hospital,Shenzhen Institute of Translational Medicine,Shenzhen 518035,Guangdong,China
    2.Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors,Shenzhen 518035,Guangdong,China
    3.Shantou University Medical College,Shantou 515041,Guangdong,China
    4.School of Basic Medical Sciences,Shenzhen University Health Science Center,Shenzhen 518060,China
  • Received:2022-09-30 Revised:2023-02-01 Online:2023-09-14 Published:2023-08-31
  • Contact: Yuchen LIU

CRISPR-Cas9系统在肿瘤生物学中的应用及前景

马孟丹1,2,3, 尚梦宇1,2,4, 刘宇辰1,2   

  1. 1.深圳大学第一附属医院,深圳市第二人民医院,深圳转化医学研究院,广东 深圳 518035
    2.广东省泌尿生殖肿瘤系统生物学与合成生物学重点实验室,广东 深圳 518035
    3.汕头大学医学院,广东 汕头 515041
    4.深圳大学医学部基础医学院,广东 深圳 518060
  • 通讯作者: 刘宇辰
  • 作者简介:马孟丹(1997—),女,硕士研究生。研究方向为医学合成生物学。E-mail:mamengdan7@163.com
    刘宇辰(1988—),男,副研究员,研究生导师,博士后合作导师。研究方向为(1)肿瘤生物治疗和医学合成生物学;(2)创新肿瘤治疗新方法;(3)构建人工基因线路,肿瘤精准治疗。E-mail:liuyuchenmdcg@163.com
  • 基金资助:
    国家重点研发计划(2021YFA0911600)

Abstract:

The RNA-directed CRISPR-Cas nuclease system was first discovered in bacteria as part of the adaptive immune system, and its ability to modify genetic components has led to a variety of practical applications, such as base editing, insertion or deletion of long segments, transcriptional regulation, and epigenetic modification. Because CRISPR-Cas gene editing tool is not only powerful, but also highly specific and efficient, it can accurately and rapidly screen the whole genome and facilitate gene therapy for specific diseases, so that it has been widely used in related research on the treatment of human diseases. The occurrence of tumor is the result of malignant degeneration of normal cells caused by the combined action of multiple factors, multiple stages and multiple mechanisms. CRISPR-Cas gene editing technology can accurately change genetic information at the DNA level and simulate the corresponding malignant characteristics of cells caused by the change of genetic information, thus becoming a molecular mechanism to explore the occurrence, development and metastasis of tumors. To investigate signaling pathways related to drug resistance in tumors and develop potential approaches to gene and cell therapy for tumor therapy. From early acquisition of oncogene mutations to metastatic colonization of distant tissues and the development of drug resistance, this continuous process leaves clear phylogenetic signatures at each step. Mapping detailed cancer cell lineages using the CRISPR gene-editing tool can reveal the dynamic processes behind the development and progression of cancer metastases, which will help track tumor development patterns. Despite its rapid development, CRISPR-Cas system still has limitations in its delivery efficiency, safety, and off-target effects in tumor therapy. The progress of CRISPR-Cas9 as a cancer research tool is reviewed. The research progress of this technique in establishing tumor model, studying the mechanism of tumor development, diagnosis, treatment and lineage tracking of tumor development was summarized. The development prospects of this technology in the new hot areas of cancer research and precision medicine in clinical medicine were discussed, and the technical challenges and future development directions were pointed out. {L-End}

Key words: CRISPR-associated protein, CRISPR-Cas derivatives, lineage tracking, cancer diagnosis, tumor therapy, screening drug targets

摘要:

RNA引导的CRISPR-Cas核酸酶系统最初作为适应性免疫系统的一部分在细菌中被发现,其修改或修饰遗传成分的能力已经带来了各种实际应用,如碱基编辑、转录调控和表观遗传修饰等。由于CRISPR-Cas基因编辑工具不仅功能强大,而且具有特异性强、效率高等特点,可以准确、快速地对整个基因组进行筛选,便于对特定疾病进行基因治疗,已被广泛应用于人类疾病治疗的相关研究。在肿瘤研究领域,CRISPR-Cas系统可以用来编辑基因组,探索肿瘤发生、发展和转移的机制。文章阐述了CRISPR-Cas9系统作为癌症研究工具所取得的进展;总结了该技术在癌症基础研究、诊断和治疗中的应用现状;讨论了这一技术在肿瘤研究新热点领域和临床医学精准医疗方面的发展前景,并指出了其面临的技术挑战和未来的发展方向。

关键词: CRISPR相关蛋白, CRISPR-Cas衍生工具, 谱系追踪, 癌症诊断, 肿瘤治疗, 筛选药物靶点

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