Ali Wajahat, Wang Fu
Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China.
Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China.
Biotechnol Adv. 2025 Mar-Apr;79:108518. doi: 10.1016/j.biotechadv.2025.108518. Epub 2025 Jan 9.
Gene circuits, which are genetically engineered systems designed to regulate gene expression, are emerging as powerful tools in disease theranostics, especially in mammalian cells. This review explores the latest advances in the design and application of gene circuits for detecting and treating various diseases. Synthetic gene circuits, inspired by electronic systems, offer precise control over therapeutic gene activity, allowing for real-time, user-defined responses to pathological signals. Notable applications include synZiFTRs for T-cell-based cancer therapies, immunomagnetic circuits for combating antibiotic-resistant infections like MRSA, and caffeine-induced circuits for managing type-2 diabetes. Additionally, advanced designs such as TetR-Elk1 circuits for reversing insulin resistance, RNAi circuits for targeting cancer cells, and synthetic circuits for managing metabolic conditions like urate homeostasis and diet-induced obesity are highlighted. These gene circuits, tailored for mammalian cells, showcase immense potential in gene- and cell-based therapies for complex metabolic and immune-related disorders, paving the way for precise, customizable treatments. The review focuses on the use of these circuits in mammalian systems and emphasizes their therapeutic implications, offering insights into future developments in disease treatment.
基因回路是旨在调控基因表达的基因工程系统,正成为疾病诊疗中的强大工具,尤其是在哺乳动物细胞中。本综述探讨了用于检测和治疗各种疾病的基因回路在设计和应用方面的最新进展。受电子系统启发的合成基因回路能够对治疗性基因活性进行精确控制,从而实现对病理信号的实时、用户定义的响应。值得注意的应用包括用于基于T细胞的癌症治疗的synZiFTRs、用于对抗如耐甲氧西林金黄色葡萄球菌等抗生素耐药感染的免疫磁回路,以及用于管理2型糖尿病的咖啡因诱导回路。此外,还重点介绍了诸如用于逆转胰岛素抵抗的TetR-Elk1回路、用于靶向癌细胞的RNAi回路,以及用于管理如尿酸稳态和饮食诱导肥胖等代谢状况的合成回路等先进设计。这些针对哺乳动物细胞定制的基因回路在针对复杂代谢和免疫相关疾病的基因和细胞疗法中展现出巨大潜力,为精确、可定制的治疗铺平了道路。该综述聚焦于这些回路在哺乳动物系统中的应用,并强调其治疗意义,为疾病治疗的未来发展提供见解。