Chinese Medical Sciences Journal ›› 2018, Vol. 33 ›› Issue (4): 240-251.doi: 10.24920/003483

• 综述 • 上一篇    下一篇

合成生物传感器在疾病检测领域的应用技术进展: 设计、分类和展望

陈雪,吕毅,吴荣谦   

  1. 精准外科与再生医学国家地方联合工程研究中心,陕西省再生医学与外科工程研究中心,先进外科技术与工程研究所,西安交通大学第一附属医院,西安,710061中国
  • 收稿日期:2018-06-07 接受日期:2018-08-17 出版日期:2018-12-30 发布日期:2018-10-08

Current Technologies of Synthetic Biosensors for Disease Detection: Design, Classification and Future Perspectives

Chen Xue,Lv Yi,Wu Rongqian   

  1. National-Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061 China
  • Received:2018-06-07 Accepted:2018-08-17 Published:2018-12-30 Online:2018-10-08

摘要:

合成生物学通过在细胞中整合入功能性的基因网络,从而赋予细胞新的功能。合成生物学领域的科学家们通过过表达,阻断和重排等手段,重新编辑细胞的天然基因通路,使其完成多样的生物学功能,并应用在诸多领域,如药物筛选,生物制药,基因治疗和组织工程等等。本文重点综述目前合成生物传感器技术在疾病筛查领域的应用。我们首先介绍了合成生物传感器设计思路和方法,之后分别对简单合成生物传感器,即对单一输入信号做出相应反应的合成生物传感器,和复杂生物传感器,即对多个输入信号做出相应反应的合成生物传感器,包括布尔门生物传感器,级联放大生物传感器,延时生物传感器,振荡器生物传感器,滞后生物传感器的设计特点和应用做了介绍。尽管合成生物感受器在疾病检测方面已展现了巨大的潜在优势,但这一技术依旧处在其发展的最初阶段。在识别和构建更多的疾病相关调控系统方面有待深入研究,同时需要在设计过程中利用计算机工具进一步提高合成生物传感器的精准性。合成生物感受器的最终发展目标是成为一种将疾病诊断作为输入和疾病治疗效果作为输出的感应-效应装置,从而为将来细胞及基因水平的治疗提供一体化的诊断和治疗解决方案。

关键词: 合成生物传感器, 基因线路, 疾病检测

Abstract:

Synthetic biology aims to endow living cells with new functions by incorporating functional gene networks into them. By overexpressing, blocking and rewiring native gene pathways, synthetic biologists have harnessed this promising technology to reprogram cells to perform diverse tasks such as drug discovery, biopharmaceutical manufacturing, gene therapy and tissue engineering, etc. In this review, we focus on current technologies of synthetic biosensors for disease detection. We start with the design principle of synthetic biosensors. Then we move towards the characteristics of simple synthetic biosensors, which can respond to a single input signal, and complex synthetic biosensors including Boolean gate biosensors, cascade biosensors, time-delay biosensors, oscillator biosensors and hysteretic biosensors, which can respond to more than two input signals and perform complex tasks. Synthetic biosensor has showed great potential in disease detection, but it is still in its infancy stage. More efforts should be made in identifying and constructing clinically relevant regulation systems. Computational tools are also needed in the design process in order to guarantee the precision of the synthetic biosensor. The ultimate goal of a synthetic biosensor is to act as a therapeutic sensor-effector device that connects diagnostic input with therapeutic output and therefore provides all-in-one diagnostic and therapeutic solutions for future gene- and cell-based therapies.

Key words: synthetic biosensor, gene circuit, disease detection

补充说明: 本文系统综述了不同类型合成生物传感器的设计原理以及在疾病诊疗方面的最新应用,包括免疫调控、肝损伤、胰岛素抵抗、Grave's病、以及尿酸内稳态等方面。

基金资助: 国家自然科学基金(81770491)

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