合成生物学在疾病信息记录与实时监测中的应用潜力

doi:10.12211/2096-8280.2022-058

合成生物学 ›› 2023, Vol. 4 ›› Issue (2): 301-317.doi: 10.12211/2096-8280.2022-058

合成生物学在疾病信息记录与实时监测中的应用潜力

马孟丹¹^,²^,³, 刘宇辰¹^,²

^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

收稿日期:2022-10-21 修回日期:2022-12-29 出版日期:2023-04-30 发布日期:2023-04-27
通讯作者: 刘宇辰
作者简介:马孟丹（1997—），女，硕士研究生。主要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。主要研究方向：（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)

Potential application of synthetic biology in disease information recording and real-time monitoring

Mengdan MA¹^,²^,³, Yuchen LIU¹^,²

^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

Received:2022-10-21 Revised:2022-12-29 Online:2023-04-30 Published:2023-04-27
Contact: Yuchen LIU

摘要/Abstract

摘要：

实时、高效和动态地改变储存在基因组中信息的能力是研究细胞生物学、控制细胞表型、监测疾病发展进程、研究原位生物学的一大技术进步。CRISPR-Cas系统的最新研究进展推动了体内DNA和RNA的精确编辑，复杂多变的基因线路使细胞工程化改造成为可能。DNA具有强大的储存信息的能力，可稳定保存数千年，在体内利用DNA记录分子事件是监测细胞信号变化和协调细胞行为的关键技术，能将细胞的瞬时信号转化为可持续反应，并永久保存下来。利用该技术，研究人员能更深入地了解在健康和疾病状态下从基因型到表型转变、临床中患者的疾病发生和用药反应情况、检测生产生活环境的变化。本文概述了合成生物学在DNA存储和细胞实时监测中的技术和应用，以及CRISPR-Cas系统在活细胞中处理和记录各种信息的优势，最后展望了它们在疾病研究和治疗方面的前景和挑战。

关键词: 合成生物学, DNA存储, 细胞实时监测记录系统, 疾病信息记录, CRISPR-Cas系统

Abstract:

The ability to change information stored with genome in real time, efficiently, and dynamically is a major technological advance for in situ studies of cell biology and biology as well to control cell phenotype, and monitor disease progression. Since it was first used for mammalian gene editing, CRISPR-Cas technology has been widely used in research, medicine development and industrial production. In addition to indel mutations induced by Cas9 activity, recent advances in CRISPR-Cas have enabled DNA or RNA base to be edited more efficiently, and synthetic biologists are developing devices for information storage by harnessing the versatilities of CRISPR-Cas-based tools and gene circuits to engineer cells with modifications. DNA has a strong ability to store information that is stable for thousands of years. Key technology for monitoring cell signal change and behavior coordination is to use DNA as the recorder of molecular events in the body, which can transfer transient signals in cells into sustainable reactions, and store them permanently. With this key technology, researchers could get an in-depth understanding on transformation from genotype to phenotype in health and disease states, drug reactions with diseases in clinical trials for patients, and environmental changes associated with activities of human being. The goal of synthetic biology is to engineer cells with genetic circuits for new biological functions. CRISPR-Cas based tools are useful in developing genetic circuits because they can be easily repurposed by designing complementary gRNAs that interfere or act on any arbitrary nucleic acid sequence of interest. Although they are still in their infancy, CRISPR-Cas based tools are gaining popularity in encoding biological memory and tracing and forwarding genetic screening for each formed lineage. In this article, we summarize the progress and application of synthetic biology in DNA storage and real-time monitoring in cell, as well as the advantages of the CRISPR-Cas system processes and records of information in living cells. Finally, we highlight their prospects and challenges in research on diseases and treatments.

Key words: synthetic biology, DNA store, real-time monitoring and recording systems in cell, disease information records, CRISPR-Cas systems

中图分类号:

马孟丹, 刘宇辰. 合成生物学在疾病信息记录与实时监测中的应用潜力[J]. 合成生物学, 2023, 4(2): 301-317, doi: 10.12211/2096-8280.2022-058.

Mengdan MA, Yuchen LIU. Potential application of synthetic biology in disease information recording and real-time monitoring[J]. Synthetic Biology Journal, 2023, 4(2): 301-317, doi: 10.12211/2096-8280.2022-058.

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记录装置系统		种群分布vs单细胞记录	写入周期	记录能力	发生顺序	持续时间	灵敏度	保真度
双稳态开关		种群	短	一般	否	是	低	低
DNA重组酶技术		种群	长	一般	否	否	低	低
ssDNA编辑技术	HiSCRIBE^[25]	种群	长	强	否	是	一般	高
CRISPR系统	Record-seq^[38]	种群	长	强	是	是	高	高
	CAMERA^[39]	单细胞	长	强	是	是	高	较高
	DNA typewriter^[40]	种群	长	强	是	是	高	高
	LINNAEUS^[41]	种群	短	弱	否	否	一般	低
	mSCRIBE^[42]	单细胞	长	强	是	是	高	高
	iTracer^[43]	单细胞	长	强	是	是	高	高
	DOMINO^[44]	种群	长	强	否	否	一般	一般

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合成生物学在疾病信息记录与实时监测中的应用潜力

Potential application of synthetic biology in disease information recording and real-time monitoring

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