Remote-Controlled Genetic Circuits: Light, Ultrasound, and Magnetic Fields for Programmable Gene Regulation.

Remote-controlled genetic circuits use externally applied physical signals to regulate gene expression and cellular functions with spatial and temporal precision. Light, ultrasound, and magnetic fields provide complementary advantages in controllability, tissue accessibility, and biological compatibility, but their performance depends on both physical-field propagation and efficient conversion of external energy into intracellular signals and predictable gene-regulatory outputs. This review presents a unified framework of physical transduction, biological sensors, signal processors, and genetic effectors for comparing prokaryotic and eukaryotic systems. Core genetic circuits are distinguished from delivery and auxiliary platforms that support cargo release, cellular uptake, or energy conversion without directly regulating genes. Representative systems are compared by circuit architecture, transduction mechanism, stimulus parameters, dynamic range, basal leakage, response kinetics, reversibility, in vivo actuation, delivery requirements, and safety. The evolution from inducible switches toward multi-input logic, tunable regulation, genetic memory, and feedback control is discussed. An end-to-end codesign workflow and modality-specific reporting framework are proposed to integrate physical inputs, transducers, genetic circuits, delivery strategies, and stimulation devices. Quantitative benchmarking and standardized safety evaluation are essential for advancing these systems toward predictable and clinically translatable therapeutic platforms.