Optogenetics for transcriptional programming and genetic engineering.

Optogenetics combines genetics and biophotonics to enable noninvasive control of biological processes with high spatiotemporal precision. When engineered into protein machineries that govern the cellular information flow as depicted in the central dogma, multiple genetically encoded non-opsin photosensory modules have been harnessed to modulate gene transcription, DNA or RNA modifications, DNA recombination, and genome engineering by utilizing photons emitting in the wide range of 200–1000 nm. We present herein generally applicable modular strategies for optogenetic engineering and highlight latest advances in the broad applications of opsin-free optogenetics to program transcriptional outputs and precisely manipulate the mammalian genome, epigenome, and epitranscriptome. We also discuss current challenges and future trends in opsin-free optogenetics, which has been rapidly evolving to meet the growing needs in synthetic biology and genetics research. Naturally evolved or engineered photosensory modules have been harnessed for transcriptional control and genetic engineering in space and time by using photons emitting in the wide range of 200–1000 nm. Optogenetic modules can be modularly engineered into host cells to control physiological processes via light-switchable allosteric control, oligomeric transition, protein–protein heterodimerization, and self-cleavage. Optogenetic devices can be integrated with the transcriptional machinery, DNA recombinases, RNA-binding proteins, and CRISPR-based genome-engineering tools to precisely manipulate transcriptional reprogramming, DNA/RNA modifications, genetic recombination, and genome/epigenome editing. Optogenetics can be combined with synthetic biology, biophotonics, and genome-engineering approaches to advance precision medicine and personalized therapies for human diseases. [ABSTRACT FROM AUTHOR]