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REVIEW

Advancements in genetic circuits as part of intelligent biotherapy for the treatment of bladder cancer: A review

Chu Liu1† ,  Junlin Lu1† ,  Jiajian Lai1 ,  Kaiwen Jie1 ,  Tianxin Lin1 ,  Haifeng Wang2* ,  Xu Chen1*
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1 Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
2 Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China
Bladder, e21200032 https://doi.org/10.14440/bladder.2024.0044
Submitted: 8 October 2024 | Revised: 19 November 2024 | Accepted: 26 December 2024 | Published: 4 February 2025
© 2025 by the Bladder published by POL Scientific. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Background: 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. Objective: 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.” Conclusion: The gene circuit can identify multiple signals, processing complex information, and generating multiple effects, thus providing a new approach for personalized treatment of tumors.

Keywords
Bladder cancer
Genetic circuits
Biotherapy
Precise therapy
Funding
This study was supported by the National Natural Science Foundation of China (grant numbers 82322056, 82273421, 82072827, and 82403733); the Science and Technology Program of Guangzhou (grant numbers 2024B03J1234, 2023A03J0718, 2024A04J6558, and 2023A1515110957); and the Postdoctoral Fellowship Program of the China Postdoctoral Science Foundation (grant number GZC20233266).
Conflict of interest
The authors declare no conflicts of interest.
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