Genome editing is a high promising biotech for correcting pathogenic mutations and trial improvement，and is widely used in basic and applicable researches. However, the true off-target rate of this technology has long been controversial, which has seriously hindered its development. In March 2019, two scientific reports led by Yang Hui and Gao Caixia, respectively, finally revealed the mystery of off-target, and both studies published in Science. Both of the mouse and rice studies consistently found that the cytosine editor causes severe point mutations, while the adenine editor and the classic CRISPR/Cas9 have no significant off-target effects. This article reviews why the off-target suspects has been long remain unsolved, andhow the latest researches achieve in precise off-target detection and
obtain very rigorous data and conclusions, which base on constructing rigorous experimental controls. At the same time, it was discussed here that humans must be cautious in conducting human clinical trials before the risks are truly eliminated.
