《生命科学》 2019, 31(4): 332-342

肿瘤细菌疗法迎来合成生物学时代

董宇轩#，曾正阳#，夏　霖，刘陈立*

(中国科学院深圳先进技术研究院合成生物学研究所，深圳 518055)

摘　要：摘　要：早于放疗、化疗等经典肿瘤疗法，细菌疗法的临床应用在1868 年就已被报道。虽然细菌拥有天然的肿瘤靶向能力、侵袭能力和细胞毒性，种类繁多且可塑性强，然而，由于其作用机理不清、可控性弱、安全性差等诸多问题，限制了它作为肿瘤治疗药物的开发和应用。近年来，合成生物学的兴起为肿瘤细菌疗法赋予了新的希望，让它重新回到了人们的视野。合成基因线路的研究( 如自杀开关、群体感应线路、振荡器和记忆线路等) 有助于实现细菌结构重塑、毒性降低、靶向性增强、表型时空可控等特性，从而提高人们对细菌疗法的操控能力。该文概述细菌疗法的发展历程，介绍合成细菌诊疗肿瘤的重要成果，探讨如何利用合成生物学手段重编程细菌，深度优化肿瘤细菌疗法。

Bacterial anti-cancer therapy in the era of synthetic biology

DONG Yu-Xuan#， ZENG Zheng-Yang#， XIA Lin， LIU Chen-Li*

(Institute of Synthetic Biology， Shenzhen Institute of Advanced Technology，
    Chinese Academy of Sciences， Shenzhen 518055， China)

Abstract: Abstract: Bacteria have been recognized and exploited as the tumor killer since the year of 1868， because of its tumor targeting and penetration abilities， but their potential as therapeutics has not been fully exploited in Western medicine because of challenges such as high virulence and low efficacy. An increasing concern related to the prevailing therapies has heightened interest in bacterial anti-cancer therapy and the development of strategies to overcome its natural limits. Recent progress in synthetic biology allowed scientists to refactor the bacterial characteristics by employing synthetic genetic circuits such as kill switches， quorum sensing circuits， oscillators and memory circuits. These new strategies may have the potential to accelerate the construction of ideal bacterial strains with superior therapeutic potential. Here， we discuss the study history of bacteria as cancer therapeutics， as well as how bacterial anti-cancer therapy evolve in the era of synthetic biology.