In natural evolution,cells need to sense various internal and external signals,then process them and execute different functions to adapt environmental changes,the process of which is completed by signal pathways composed of molecules naturally existing in cells.Gene circuits are artificial signal pathways tailored by synthetic biology using engineered or de novo designed biomolecules to realize spe-cific aims like detection or treatment.Gene ciruits consist of 3 components:sensors,prcessors,and actu-ators.After rational design,gene circuits can sense tumor biomarkers or unbalanced pathological condi-tions,then release tracer molecules or toxic products to identify or kill tumor cells.These tailored gene circuits exhibited unprecedented specificity in both bacteria and human cells,which has been used to treat cancer in animal experiments.There are 3 approaches when applying gene circuits in cancer treat-ment:cancer-targeting bacteria based therapies,CAR-T based therapies,and nucleic acid based thera-pies.Optimization of gene circuits mainly focus on the modularity,orthogonality,adjustability,and com-posability,in the process of which protein circuits exhibited obvious advantages.They have high reaction rates,excellent composability,and never cause permanent gene changes.The design of gene circuits with multiple sensors and cybernetics-guided design are 2 major research directions of synthetic circuits.Developing sophisticated single transcript protein circuits with multiple sensors and regulators enables new generations of programmable synthetic devices.Here we reviewed the progression of gene circuits in the detection and treatment of cancer,particularly focusing on the application of protease and corresponding cut sites in the design of gene circuits.The flexibility of gene circuit regulation made the design of protein circuits possible,providing ideas for the research of new generation of gene circuits.
NETL
NSTL
万方数据
