《生命科学》 2021, 33(12): 1520-1531

合成生物学在慢病防治领域的应用与展望

管宁子 , 尹剑丽 , 王义丹 , 余贵玲 , 叶海峰^*

华东师范大学生命科学学院，上海市调控生物学重点实验室，华东师范大学医学合成生物学研究中心，上海 200241

摘　要：

随着合成生物学各项技术的日益完善和遗传元件的逐渐丰富，越来越多的基于不同响应机理、不同逻辑运算的人工基因线路被陆续设计开发。基于人工基因线路的定制化细胞疗法和基因治疗极大地推动了重大疾病的创新治疗策略并显示出巨大潜力。然而，目前基因线路定制细胞的设计与构建仍主要依靠假设-试错循环的经验性方法。如何设计与构建智能化、自动化的定制细胞和基因线路以满足不同实际应用场景需求是目前亟需解决的瓶颈问题。未来的合成生物学发展，将利用蛋白质定向进化技术、人工智能化技术在解析底盘细胞生命活动分子机制的基础上，设计动态化感知的智能化基因线路，有效地保证癌症、代谢疾病等治疗的安全性、高效性和特异性。

通讯作者：叶海峰 , Email:hfye@bio.ecnu.edu.cn

Application and prospect of synthetic biology in the prevention and treatment of chronic diseases

GUAN Ning-Zi , YIN Jian-Li , WANG Yi-Dan , YU Gui-Ling , YE Hai-Feng^*

Biomedical Synthetic Biology Research Center, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China

Abstract:

With the improvement of synthetic biology technology and the enrichment of genetic elements, more and more synthetic genetic circuits based on different response mechanisms and logic computations have been designed and developed. Customized cell therapies and gene therapies based on synthetic genetic circuits have greatly driven innovative treatment strategies for severe diseases and show great potential. However, at present, the design and construction of customized cells with genetic circuits mainly rely on the empirical methods of hypothesis-trial-error cycles. How to design and construct intelligent and automated customized cells and genetic circuits to meet the requirements of different application scenarios is a bottleneck that needs to be solved urgently. In the future development of synthetic biology, protein directed evolution and artificial intelligence technologies will be introduced to design intelligent genetic circuits with dynamic sensing on the basis of analyzing the molecular mechanism of chassis cells life, so as to effectively enhance the safety, efficiency and specificity of therapies for cancer, metabolic diseases and so on.

Communication Author：YE Hai-Feng , Email:hfye@bio.ecnu.edu.cn