Advancement in synthetic gene circuits engineering: An alternative strategy for microRNA imaging and disease theranostics

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.