Development and application of light-controlled inducible recombination systems.

The site-specific recombination systems are composed of recombinases and specific recognition sites, which are powerful tools for gene manipulation and have been extensively used in life sciences research. Inducible recombination systems have been developed to precisely regulate gene expression in a spatiotemporal manner in cells and animals for applications such as gene function research, cell lineage tracing and disease treatment. Based on different spatiotemporal expression methods of recombinases, inducible recombination systems can be divided into two categories: chemical- controlled and light-controlled inductions. Light-controlled inducible recombination systems that utilize light as inducer consist of photocage and optogenetics in accordance with optical control patterns and objects. Photocaged inducible recombination systems are using photosensitive groups to control chemical inducers or recombinases. Their activities are inhibited by photosensitive groups before light induction and recovered after specific light irradiation, leading to light-controlled inducible gene recombination. While optogenetic inducible recombination systems rely on reactivations of split recombinases that mediated by optogenetic switches. Optogenetic switches are composed of a series of gene-encoded photosensitive proteins, including cryptochromes, VIVID, phytochromes, etc. These types of light-controlled inducible recombination systems provide more possibilities for analyzing gene expression and function from the dimension of high spatiotemporal resolution to meet the increasingly complex demands of life science research. In this review, we summarize the developing principles and applications of different types of light-controlled inducible recombination systems, compare their advantages and disadvantages, and prospect the development of more light-controlled recombination systems in the future, with the aims to provide theoretical basis and guidance for system optimization and upgrade.