光遗传学照进生物医学研究进展

Synthetic biology enables rational design of regulatory molecules and circuits to reprogram cellular behaviors, and its applications to human cells could lead to powerful gene- and cell-based therapies, which are well recognized as central pillars of next-generation medicines. However, the safety of these therapies remains to be assessed, and controllability is a critical issue affecting their safety and limiting their clinical applications. In recent years, optogenetic technologies have been widely used in biomedical applications, which provides new insights for treating intractable diseases due to their distinguishing features of non-invasiveness, reversibility, and spatiotemporal resolution. Light is an ideal inducer to control gene expression, enabling precise and spatiotemporal manipulation of gene expression and cell behaviors by illuminating with light of appropriate intensity and wavelength as a triggering signal to achieve pinpoint spatiotemporal control of cellular activities. With the development of optogenetic toolkits, optogenetics has recently been developed for therapeutic applications. In this review, we summarize various optogenetic tools responsive to different wavelengths and their applications for precise treatment of neurological diseases, tumors, cardiovascular diseases, diabetes, enteric diseases as well as for the optogenetic control of gene transcription, gene editing, gene recombination and organelle movement. At the same time, we introduce recent research progress in portable bioelectronic medicine and artificial intelligence-assisted diagnosis and treatment systems, which are based on optogenetic techniques and the intelligent electronic devices. The rapid development of optogenetics has enormously extended the scope of traditional bioelectronic medicine, and the remote-controllability, reversibility, and negligible toxicity of optical control systems provide a solid foundation for the application of optogenetics in biomedicine. The success of these approaches would have an impact on precision medicine in the future practice. Finally, we also discuss the shortcomings of existing optogenetic tools and the challenges that would be faced in the future clinical applications as well as the prospects of their development.