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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
Received:30 September 2022,
Revised:2023-02-01,
Published:31 August 2023
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马孟丹, 尚梦宇, 刘宇辰. CRISPR-Cas9系统在肿瘤生物学中的应用及前景[J]. 合成生物学, 2023, 4(4): 703-719
MA Mengdan, SHANG Mengyu, LIU Yuchen. Application and prospect of CRISPR-Cas9 system in tumor biology[J]. Synthetic Biology Journal, 2023, 4(4): 703-719
马孟丹, 尚梦宇, 刘宇辰. CRISPR-Cas9系统在肿瘤生物学中的应用及前景[J]. 合成生物学, 2023, 4(4): 703-719 DOI: 10.12211/2096-8280.2022-054.
MA Mengdan, SHANG Mengyu, LIU Yuchen. Application and prospect of CRISPR-Cas9 system in tumor biology[J]. Synthetic Biology Journal, 2023, 4(4): 703-719 DOI: 10.12211/2096-8280.2022-054.
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。
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.
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