Perspectives on synthetic protein circuits in mammalian cells

IF 4.7 3区 工程技术 Q2 ENGINEERING, BIOMEDICAL Current Opinion in Biomedical Engineering Pub Date : 2024-08-14 DOI:10.1016/j.cobme.2024.100555
Carlos A. Aldrete , Connie An , Connor C. Call , Xiaojing J. Gao, Alexander E. Vlahos
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Abstract

Mammalian synthetic biology aims to engineer cellular behaviors for therapeutic applications, such as enhancing immune cell efficacy against cancers or improving cell transplantation outcomes. Programming complex biological functions necessitates an understanding of molecular mechanisms governing cellular responses to stimuli. Traditionally, synthetic biology has focused on transcriptional circuits, but recent advances have led to the development of synthetic protein circuits, leveraging programmable binding, proteolysis, or phosphorylation to modulate protein interactions and cellular functions. These circuits offer advantages including robust performance, rapid functionality, and compact design, making them suitable for cellular engineering or gene therapies. This review outlines the post-translational toolkit, emphasizing synthetic protein components utilizing proteolysis or phosphorylation to program mammalian cell behaviors. Finally, we focus on key differences between rewiring native signaling pathways and creating orthogonal behaviors, alongside a proposed framework for translating synthetic protein circuits from tool development to pre-clinical applications in biomedicine.

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哺乳动物细胞中合成蛋白质回路的前景
哺乳动物合成生物学旨在为治疗应用设计细胞行为,如提高免疫细胞对癌症的疗效或改善细胞移植效果。要编程复杂的生物功能,就必须了解细胞对刺激做出反应的分子机制。传统上,合成生物学的重点是转录电路,但最近的进展导致了合成蛋白质电路的发展,利用可编程的结合、蛋白水解或磷酸化来调节蛋白质相互作用和细胞功能。这些电路具有性能稳定、功能快速、设计紧凑等优点,适合用于细胞工程或基因治疗。本综述概述了翻译后工具包,强调了利用蛋白水解或磷酸化来编程哺乳动物细胞行为的合成蛋白元件。最后,我们将重点讨论重新连接本地信号通路与创造正交行为之间的主要区别,并提出一个将合成蛋白质电路从工具开发转化为生物医学临床前应用的框架。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Opinion in Biomedical Engineering
Current Opinion in Biomedical Engineering Medicine-Medicine (miscellaneous)
CiteScore
8.60
自引率
2.60%
发文量
59
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