A major aim in the field of synthetic biology is developing tools capable of responding to user-defined inputs by activating therapeutically relevant cellular functions. Gene transcription and regulation in response to external stimuli are some of the most powerful and versatile of these cellular functions being explored. Motivated by the success of chimeric antigen receptor (CAR) T-cell therapies, transmembrane receptor-based platforms have been embraced for their ability to sense extracellular ligands and to subsequently activate intracellular signal transduction. The integration of transmembrane receptors with transcriptional activation platforms has not yet achieved its full potential. Transient expression of plasmid DNA is often used to explore gene regulation platforms . However, applications capable of targeting therapeutically relevant endogenous or stably integrated genes are more clinically relevant. Gene regulation may allow for engineered cells to traffic into tissues of interest and secrete functional proteins into the extracellular space or to differentiate into functional cells. Transmembrane receptors that regulate transcription have the potential to revolutionize cell therapies in a myriad of applications, including cancer treatment and regenerative medicine. In this review, we will examine current engineering approaches to control transcription in mammalian cells with an emphasis on systems that can be selectively activated in response to extracellular signals. We will also speculate on the potential therapeutic applications of these technologies and examine promising approaches to expand their capabilities and tighten the control of gene regulation in cellular therapies.

中文翻译：

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细胞疗法的工程转录调控

合成生物学领域的一个主要目标是开发能够通过激活治疗相关的细胞功能来响应用户定义的输入的工具。响应外部刺激的基因转录和调节是正在探索的这些细胞功能中最强大和最通用的功能之一。受嵌合抗原受体 (CAR) T 细胞疗法成功的推动，基于跨膜受体的平台因其感知细胞外配体并随后激活细胞内信号转导的能力而受到欢迎。跨膜受体与转录激活平台的整合尚未充分发挥其潜力。质粒DNA的瞬时表达通常用于探索基因调控平台。然而，能够靶向治疗相关内源或稳定整合基因的应用在临床上更具相关性。基因调控可能允许工程细胞进入感兴趣的组织并将功能蛋白分泌到细胞外空间或分化成功能细胞。调节转录的跨膜受体有可能在众多应用中彻底改变细胞疗法，包括癌症治疗和再生医学。在这篇综述中，我们将研究当前控制哺乳动物细胞转录的工程方法，重点是可以选择性激活以响应细胞外信号的系统。我们还将推测这些技术的潜在治疗应用，并研究有希望的方法来扩展其能力并加强细胞治疗中基因调控的控制。