Haimei Wang

Hainan Institute of Biotechnology, Haikou, 570206, Hainan, China
Author    Correspondence author
Computational Molecular Biology, 2025, Vol. 15, No. 4   doi: 10.5376/cmb.2025.15.0019
Received: 03 Jun., 2025    Accepted: 14 Jul., 2025    Published: 02 Aug., 2025

This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Wang H.M., 2025, Mathematical modeling of synthetic genetic circuits, Computational Molecular Biology, 15(4): 193-207 (doi: 10.5376/cmb.2025.15.0019)

 

Synthetic genetic circuits are the core research objects in synthetic biology, and the programming of cell behavior is achieved through the combination of engineered gene elements. Mathematical modeling provides crucial support for understanding and designing synthetic genetic circuits, enabling researchers to predict the dynamic behavior of the circuits and guide experimental optimization. This study reviews the categories of synthetic genetic circuits (such as gene switches, oscillators, feedback circuits, etc.) and their biological mechanisms, with a focus on the application of ordinary differential equation (ODE) models, stochastic modeling, and network topology dynamics models in circuit modeling. We expounded on the estimation of model parameters, sensitivity analysis, and the integration methods of experimental data and models, and compared the characteristics of numerical simulation algorithms and commonly used software tools (such as MATLAB, COPASI, BioNetGen, etc.). Through the discussion of the steady-state, oscillation behavior, multiple steady-state and bifurcation analysis of system dynamics, the understanding of the influence of positive and negative feedback mechanisms on system stability is deepened. In addition, we took the classic synthetic gene oscillator Repressilator as a case to conduct modeling and simulation analysis, and compared the model predictions with the experimental data. Finally, the application prospects of synthetic genetic circuits in the fields of bioengineering and medicine were summarized, and the future directions of promoting the design of synthetic circuits with the help of model optimization and artificial intelligence-assisted design were prospected. Research shows that mathematical modeling and computational simulation have become key tools for the study and design of synthetic genetic circuits, providing a theoretical basis and practical guidance for the engineering transformation of complex biological systems.

Synthetic genetic circuit; Mathematical modeling; Ordinary differential equation; Gene oscillator; Feedback regulation