合成生物学 ›› 2023, Vol. 4 ›› Issue (2): 244-262.doi: 10.12211/2096-8280.2022-059
吴晓昊1, 廖荣东2, 李飞云1, 欧阳中天1, 冉怡1, 公维远1, 曲明灏1, 陈明珏1, 林荔军2, 肖国芝1
收稿日期:
2022-10-31
修回日期:
2023-02-01
出版日期:
2023-04-30
发布日期:
2023-04-27
通讯作者:
林荔军,肖国芝
作者简介:
基金资助:
Xiaohao WU1, Rongdong LIAO2, Feiyun LI1, Zhongtian OUYANG1, Yi RAN1, Weiyuan GONG1, Minghao QU1, Mingjue CHEN1, Lijun LIN2, Guozhi XIAO1
Received:
2022-10-31
Revised:
2023-02-01
Online:
2023-04-30
Published:
2023-04-27
Contact:
Lijun LIN, Guozhi XIAO
摘要:
合成生物学是一门新兴学科。从广义上讲,合成生物学是通过将基因工程、系统生物学、计算机工程等多学科作为工具,根据特定需求进行设计,乃至重新合成生物体系。近20年来,合成生物学领域的相关研究不断取得突破,并已在针对人类疾病的诊断、临床治疗、药物研发等诸多方面获得重要应用。合成生物学不仅为疾病的早期、精确诊断提供新的思路和技术手段,还发展出多种新型的疾病治疗手段,包括基于合成生物学原理设计的细胞疗法、细菌疗法、疫苗、生物医学材料等。利用合成生物学方法,我们可以精确诊断早期疾病、精准改造细胞或细菌、进行疾病机制研究和药物筛选、快速生产新型疫苗和生物医学材料。基于合成生物学的疾病诊疗方法将是科研领域重要的发展方向之一,并将在未来彻底改变临床疾病的诊疗方式。本文综述合成生物学原理和技术在疾病诊断和治疗中的应用,并进一步探讨合成生物学在疫苗生产、生物医学材料、新药研发等方面的应用。
中图分类号:
吴晓昊, 廖荣东, 李飞云, 欧阳中天, 冉怡, 公维远, 曲明灏, 陈明珏, 林荔军, 肖国芝. 合成生物学在疾病诊疗中的应用[J]. 合成生物学, 2023, 4(2): 244-262, doi: 10.12211/2096-8280.2022-059.
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, doi: 10.12211/2096-8280.2022-059.
图1
在CAR-T细胞中引入的“逻辑门”系统“与门”:当synthetic notch(SynNotch)受体识别并结合肿瘤抗原时,激活CAR的表达,由CAR识别另一肿瘤抗原后激活T细胞并介导其对肿瘤的杀伤功能(如图左上所示)。另一种“与门”:弱活化信号的CAR和共刺激受体(co-stimulatory receptor, CCR)均不足以单独提供激活T细胞的信号。当两个受体共同识别出对应肿瘤抗原时,才足以激活T细胞功能(如图右上所示)。“或门”:串联表达不同CAR的单链可变区片段(single-chain variable fragment, ScFv),任一ScFv片段识别到对应肿瘤抗原都可以激活T细胞功能(如图左下所示)。“非门”:当CAR识别到肿瘤抗原后激活T细胞,同时当inhibitory CAR(iCAR)识别到正常细胞抗原时,iCAR发出抑制信号抑制CAR的激活信号从而保护正常细胞(如图右下所示)
表2
合成生物医学材料总结
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 | [ |
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 | [ | |
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 | [ |
RNA纳米材料 | 控制体内细胞代谢过程 | [ | |
蛋白质材料 | 弹性蛋白样多肽 | 用于组织工程和药物递送 | [ |
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 | [ | |
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 | [ |
大肠杆菌ECM材料 | 生产抗肿瘤药物——脱氧紫罗兰素 | [ | |
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 | [ | |
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 | [ |
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