Research Center for Drug and Vaccine Development National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan.
The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
ACS Nano. 2023 May 23;17(10):9039-9048. doi: 10.1021/acsnano.2c11744. Epub 2023 May 8.
Cell membrane receptors regulate cellular responses through sensing extracellular environmental signals and subsequently transducing them. Receptor engineering provides a means of directing cells to react to a designated external cue and exert programmed functions. However, rational design and precise modulation of receptor signaling activity remain challenging. Here, we report an aptamer-based signal transduction system and its applications in controlling and customizing the functions of engineered receptors. A previously reported membrane receptor-aptamer pair was used to design a synthetic receptor system that transduces cell signaling depending on exogenous aptamer input. To eliminate the cross-reactivity of the receptor with its native ligand, the extracellular domain of the receptor was engineered to ensure that the receptor was solely activated by the DNA aptamer. The present system features tunability in the signaling output level using aptamer ligands with different receptor dimerization propensities. In addition, the functional programmability of DNA aptamers enables the modular sensing of extracellular molecules without the need for genetic engineering of the receptor.
细胞膜受体通过感知细胞外环境信号并将其转导来调节细胞反应。受体工程为指导细胞对指定的外部线索做出反应并发挥预定功能提供了一种手段。然而，受体信号转导活性的合理设计和精确调节仍然具有挑战性。在这里，我们报告了一种基于适体的信号转导系统及其在控制和定制工程受体功能方面的应用。使用先前报道的膜受体-适体对来设计一种合成受体系统，该系统根据外源性适体输入来转导细胞信号。为了消除受体与其天然配体的交叉反应性，对受体的细胞外结构域进行了工程改造，以确保受体仅被 DNA 适体激活。本系统的特点是使用具有不同受体二聚化倾向的适体配体来调节信号输出水平。此外，DNA 适体的功能可编程性使得能够对细胞外分子进行模块化感测，而无需对受体进行基因工程改造。
