Liu Chu, Lu Junlin, Lai Jiajian, Jie Kaiwen, Lin Tianxin, Wang Haifeng, Chen Xu
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.
Bladder (San Franc). 2025 Feb 4;12(1):e21200032. doi: 10.14440/bladder.2024.0044. eCollection 2025.
Bladder cancer poses a significant threat to human health. In recent years, genetic circuit therapy has emerged as a novel alternative for precision tumor treatment, demonstrating promising potential for clinical application. Compared to traditional drugs, genetic circuits - typically carried by plasmids - offer advantages such as modularity, druggability, and shorter drug development cycles. These circuits can identify multiple molecular signals from tumors and integrate them through logic gates to specifically target tumor cells. Furthermore, by assembling effector modules, they can induce specific forms of cell death in tumor cells or alter malignant phenotypes, thereby reshaping the immune microenvironment to produce efficient, durable, and controllable antitumor effects. The urinary system serves as an ideal model for this new therapy due to its accessibility from the outside. Several genetic circuits have already been validated for the treatment of bladder cancer. This review outlined the effectiveness and potential value of genetic circuits in bladder cancer therapy.
This review focused on the design principles of genetic circuits, their ability to recognize and convert signals, their therapeutic signal output, and the associated delivery vehicles. We also discussed the challenges and future prospects of genetic circuits as a novel form of "intelligent biotherapy."
The gene circuit can identify multiple signals, processing complex information, and generating multiple effects, thus providing a new approach for personalized treatment of tumors.
膀胱癌对人类健康构成重大威胁。近年来,基因回路疗法已成为精准肿瘤治疗的一种新型替代方法,展现出了良好的临床应用潜力。与传统药物相比,通常由质粒携带的基因回路具有模块化、可成药以及药物研发周期短等优势。这些回路能够识别来自肿瘤的多种分子信号,并通过逻辑门对其进行整合,从而特异性地靶向肿瘤细胞。此外,通过组装效应模块,它们可以诱导肿瘤细胞发生特定形式的细胞死亡或改变恶性表型,进而重塑免疫微环境,产生高效、持久且可控的抗肿瘤效果。由于泌尿系统易于从外部接触,因此它是这种新疗法的理想模型。几种基因回路已被证实可用于治疗膀胱癌。本综述概述了基因回路在膀胱癌治疗中的有效性和潜在价值。
本综述重点关注基因回路的设计原则、其识别和转换信号的能力、其治疗信号输出以及相关的递送载体。我们还讨论了基因回路作为一种新型“智能生物疗法”所面临的挑战和未来前景。
基因回路能够识别多种信号,处理复杂信息并产生多种效应,从而为肿瘤的个性化治疗提供了一种新方法。