Applications of synthetic biology in disease diagnosis and treatment

doi:10.12211/2096-8280.2022-059

Abstract

Abstract:

Synthetic biology (SB) is an emerging discipline, which utilizes genetic engineering, systems biology, computer science, and other disciplines as tools to design, and even re-synthesize biological systems for specific needs. In the past 20 years, milestone breakthroughs in SB have been achieved and applied in the diagnosis and treatment of human diseases, particularly in the discovery of new drugs. SB not only provides new ideas and technical tools for the early and accurate diagnosis of diseases, but also develops a variety of new approaches for treating diseases, including cell therapy, bacteriotherapy, vaccines, and biomedical materials. Using SB-based methods, we can precisely diagnose diseases at an early stage, specifically engineer cells or bacteria, conduct mechanistic studies and drug screening, and rapidly produce vaccines and biomedical materials. SB with the "design-build-test" cycle greatly facilitates the development of new diagnostic and therapeutic approaches. Moreover, SB applies engineering principles (modularity, composability, abstraction, and standardization) to redefine biological systems in a more modular and composable way. Through this framework, the basic units of the biological system are fully characterized as standardized motifs (DNA sequences or gene-encoded products), and these motifs are mixed and matched to construct a fully functional genetic apparatus. By utilizing recently developed gene editing tools, such as the clustered regularly interspaced palindromic repeats (CRISPR/Cas9) technology, SB can integrate programmed devices into a chassis (e.g., bacteria and yeast), create new systems capable of producing target biomolecules or behaviors, and precisely manipulate the genome of cells and individuals to repair genetic defects. SB-based disease diagnosis and treatment will be one of the important development directions in the field of scientific research to completely change the way of diagnosis and clinical treatment of diseases in the future. This article reviews the applications of SB-based technologies in disease diagnosis and treatment, as well as in the production of vaccines and biomedical materials, as well as in new drug development.

Key words: synthetic biology, disease, diagnosis, treatment, drug development

CLC Number:

Xiaohao WU, Rongdong LIAO, Feiyun LI, Zhongtian OUYANG, Yi RAN, Weiyuan GONG, Minghao QU, Mingjue CHEN, Lijun LIN, Guozhi XIAO. Applications of synthetic biology in disease diagnosis and treatment[J]. Synthetic Biology Journal, 2023, 4(2): 244-262.

Figures/Tables 5

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项目	酶传感器	质粒传感器	哺乳动物细胞传感器	细菌传感器
原始信号	酶活性失调	转录活性改变	转录或代谢活性改变	生化特性改变（如营养物质，pH等）
放大方式	催化放大尿液浓缩	分泌物增加	细胞增殖分泌物增加	细菌增殖催化放大尿液浓缩
信号特征	底物信号扩大	特异性转录	肿瘤微环境驱动信号激活	特异性肿瘤靶向浸润
检测方式	尿液，血液，呼吸	尿液，血液	尿液，血液	尿液，血液

材料种类	材料名称	材料特性	参考文献
多糖材料	细菌纤维素	高物理强度和高保水能力，可生产人造血管支架	[115]
多糖材料	纤维素-几丁质共聚物	可作为静脉假体，在动物体内能被降解	[116]
核酸材料	ssDNA纳米材料	制作病原体传感器，对动物体内的病原体进行探测	[117]
核酸材料	RNA纳米材料	控制体内细胞代谢过程	[118]
蛋白质材料	弹性蛋白样多肽	用于组织工程和药物递送	[119]
蛋白质材料	弹性蛋白样重组体	制作基于ELR的水凝胶，用于传递药物和疫苗	[120]
活细胞材料	curli纳米纤维	与生物膜融合后可结合在特定表面，用于治疗小鼠胃肠道炎症	[121]
	大肠杆菌ECM材料	生产抗肿瘤药物——脱氧紫罗兰素	[122]
	E.coli Nissle材料	一种无毒性的大肠杆菌材料，对患者进行持续给药	[123]
	枯草芽孢杆菌水凝膜	具有多功能再生和可调性，可作为潜在的医疗生物材料	[124]

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