Arber Caroline, Young Melvin, Barth Patrick
Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Curr Opin Biotechnol. 2017 Oct;47:92-101. doi: 10.1016/j.copbio.2017.06.009. Epub 2017 Jul 11.
Taking inspiration from Nature, synthetic biology utilizes and modifies biological components to expand the range of biological functions for engineering new practical devices and therapeutics. While early breakthroughs mainly concerned the design of gene circuits, recent efforts have focused on engineering signaling pathways to reprogram cellular functions. Since signal transduction across cell membranes initiates and controls intracellular signaling, membrane receptors have been targeted by diverse protein engineering approaches despite limited mechanistic understanding of their function. The modular architecture of several receptor families has enabled the empirical construction of chimeric receptors combining domains from distinct native receptors which have found successful immunotherapeutic applications. Meanwhile, progress in membrane protein structure determination, computational modeling and rational design promise to foster the engineering of a broader range of membrane receptor functions. Marrying empirical and rational membrane protein engineering approaches should enable the reprogramming of cells with widely diverse fine-tuned functions.
合成生物学从自然中汲取灵感，利用并改造生物组件以拓展生物功能的范围，用于设计新型实用装置和疗法。早期的突破主要涉及基因回路的设计，而近期的工作则聚焦于对信号通路进行工程改造以重新编程细胞功能。由于跨细胞膜的信号转导启动并控制细胞内信号传导，尽管对膜受体功能的机制了解有限，但各种蛋白质工程方法已将膜受体作为靶点。几个受体家族的模块化结构使得人们能够凭经验构建嵌合受体，这些嵌合受体结合了来自不同天然受体的结构域，并已在免疫治疗中获得成功应用。与此同时，膜蛋白结构测定、计算建模和合理设计方面的进展有望推动更广泛的膜受体功能工程。将凭经验和合理的膜蛋白工程方法相结合，应能对具有广泛多样的微调功能的细胞进行重新编程。
