Genetic manipulation technologies have revolutionized our ability to control cellular activities with high precision. Five major approaches—chemogenetics, optogenetics, odorgenetics, magnetogenetics, and sonogenetics—offer distinct advantages for different research and therapeutic scenarios. However, a unified framework for systematic comparison across these technologies has been lacking.This review provides a comprehensive analysis of these five genetic manipulation technologies from three perspectives: molecular mechanisms, quantitative performance metrics, and application scenarios. We first dissect the signaling pathways and key molecular components underlying each technology. We then establish a seven-dimensional evaluation framework encompassing spatiotemporal resolution, tissue penetration, cell-type specificity, reversibility, multiplexing capability, biosafety, and technical accessibility. Using this framework, we systematically score and compare the five technologies, revealing that optogenetics excels in spatiotemporal precision (millisecond/micrometer scale), chemogenetics offers superior clinical translatability, while sonogenetics and magnetogenetics provide advantages for non-invasive deep tissue applications. We further analyze optimal application scenarios for each technology, including neural circuit dissection, chronic disease management, and deep tissue intervention.This comparative analysis provides researchers with an evidence-based guide for technology selection. We propose that future developments should focus on hybrid approaches combining the strengths of multiple technologies, and on addressing current limitations in delivery efficiency and long-term biosafety for clinical translation.
Xiao et al. (Fri,) studied this question.