以CRISPR/Cas为代表的基因编辑技术革命性改变了生物学以及相关产业。但现有工具相对较大的尺寸使其较难递送，且大片段DNA整合的效率仍然较低。因此，在我们聚焦开发具有小尺寸和整合大片段DNA能力的新型基因编辑工具。基于数据驱动的模式，我们对原核转座子IS605家族的TnpB蛋白进行了系统研究，并鉴定出多种尺寸极小且在人类细胞中具有高活性的可编程靶向核酸酶。同时，我们从102个动物基因组中预测了130个完整的DNA转座子元件，并经功能筛选获得40种全新的具有将DNA大片段整合入人类基因组能力的转座子工具。这些成果丰富了基因工程工具箱，并且为转座子生物学研究提供了重要的功能数据和理解。

Gene editing technologies, represented by CRISPR/Cas, have significantly impacted biology and related industries. However, the relatively large size of existing tools makes their delivery challenging, and the efficiency of integrating large DNA fragments remains low. Therefore, we have focused on developing novel gene editing tools with small sizes and the ability to integrate large DNA fragments. Using a data-driven approach, we systematically studied the TnpB protein of the IS605 transposon family in prokaryotes and identified multiple miniature programmable nucleases with high activity in human cells. Additionally, we predicted 130 complete DNA transposon elements from 102 animal genomes and obtained 40 novel transposon tools with the ability to integrate large DNA fragments into the human genome through functional screening. These studies enrich the genetic engineering toolbox and provide important functional data and insights into transposon biology.