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Building sophisticated sensors of extracellular cues that enable mammalian cells to work as "doctors" in the body.
Cellular and Molecular Life Sciences ( IF 6.2 ) Pub Date : 2020-03-17 , DOI: 10.1007/s00018-020-03486-y
Ryosuke Kojima 1, 2 , Dominque Aubel 3 , Martin Fussenegger 4, 5
Affiliation  

Mammalian cells are inherently capable of sensing extracellular environmental signals and activating complex biological functions on demand. Advances in synthetic biology have made it possible to install additional capabilities, which can allow cells to sense the presence of custom biological molecules and provide defined outputs on demand. When implanted/infused in patients, such engineered cells can work as intrabody “doctors” that diagnose disease states and produce and deliver therapeutic molecules when and where necessary. The key to construction of such theranostic cells is the development of a range of sensor systems for detecting various extracellular environmental cues that can be rewired to custom outputs. In this review, we introduce the state-of-art engineering principles utilized in the design of sensor systems to detect soluble factors and also to detect specific cell contact, and we discuss their potential role in treating intractable diseases by delivering appropriate therapeutic functions on demand. We also discuss the challenges facing these emerging technologies.



中文翻译:


构建复杂的细胞外信号传感器,使哺乳动物细胞能够充当体内的“医生”。



哺乳动物细胞本质上能够感知细胞外环境信号并根据需要激活复杂的生物功能。合成生物学的进步使得安装额外的功能成为可能,这些功能可以让细胞感知定制生物分子的存在并根据需要提供定义的输出。当植入/输注到患者体内时,这种工程细胞可以充当体内“医生”,诊断疾病状态并在必要时产生和递送治疗分子。构建此类治疗诊断细胞的关键是开发一系列传感器系统,用于检测各种细胞外环境线索,这些线索可以重新连接到定制输出。在这篇综述中,我们介绍了传感器系统设计中使用的最先进的工程原理,以检测可溶性因子和检测特定的细胞接触,并讨论了它们通过按需提供适当的治疗功能来治疗难治性疾病的潜在作用。我们还讨论了这些新兴技术面临的挑战。

更新日期:2020-03-17
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