近年来，Cre/loxP重组酶系统作为位点特异性基因重组系统在功能基因研究领域占据了重要地位，但是该技术的不可控性也限制了其进一步的发展。因此，亟需开发更为精准可控的条件性基因重组系统。本项目利用合成生物学方法和光遗传学技术，开发设计远红光调控split-Cre重组酶系统，通过远红光调控split-Cre重组酶的表达，对靶基因实现安全无痕、高度时空特异性的基因编辑。首先，在我们前期远红光调控转基因表达系统基础上，结合Cre重组酶的结构特征，设计构建优化一套远红光调控split-Cre基因编辑重组酶系统，并对该系统进行多方位的基因表达动力学特征研究；其次，将该系统上载到腺相关病毒载体上，并递送到转基因报告小鼠模型中，实现小鼠体内用远红光对靶基因的精确编辑，在体内实现光控基因表达，为后续基因治疗奠定基础。通过该研究，可以为后续功能基因、命运图谱的研究、基因治疗以及动物模型的构建等提供新方法。

In recent years, the Cre/loxP recombinase system, as a site-specific gene recombination system, has occupied an important position in the field of functional gene research, but the uncontrollability of this technology has also restricted its further development. Therefore, there is an urgent need to develop a more precise and controllable conditional genetic recombination system. In this project, we mainly utilize synthetic biology approaches and optogenetics techniques to develop a far-red light-regulated split-Cre recombinase system, which can be used to regulate the expression of the split-Cre recombinase by far-red light to achieve safe, traceless, and highly spatial temporal specific of gene editing. Firstly, based on our far red light-regulated transgene expression system published earlier, combined with the structural characteristics of Cre recombinase, we designed and optimized a far-red light regulated split-Cre gene editing recombinase system, and will study the multi-directional gene expression kinetics of the system. Secondly, the system was uploaded onto an adeno-associated virus vector and delivered to a transgenic reporter mouse model to achieve precise editing of the target gene with far-red light in mice, and to achieve light-controlled gene expression in vivo. This system will lay the foundation for the subsequent gene therapy. In summary, this research can provide new methods for gene function research, the study of fate maps, gene therapy and the construction of animal models in the near future.