%0 Journal Article
%T Lb2Cas12a and its engineered variants mediate genome editing in human cells.
%A Liu X
%A Lin L
%A Tang L
%A Xie H
%A Gu L
%A Lv X
%A Liu C
%A Zhao J
%A Deng R
%A Liu Y
%A Qu J
%A Gu F
%J FASEB J
%V 35
%N 4
%D 04 2021
%M 33715215
%F 5.834
%R 10.1096/fj.202001013RR
%X Cas12a-mediated targeted genome engineering strategies have enabled a broad range of research and clinical applications. However, the limited target-selection spectrum and low activity/fidelity remain a bottleneck for its widespread application in precision site-specific human genome editing. Therefore, there exists an acute need to identify novel Cas12a nucleases with improved features for genome editing. By screening a range of candidate Cas12a nucleases, here we demonstrate that Lb2Cas12a possesses genome editing activity in human cells and it has greater flexibility in PAM (5'-BYYV-3') selection. Furthermore, we engineered Lb2Cas12a to generate variants (Lb2Cas12a-RVR and Lb2Cas12a-RR), which greatly expands the target-selection spectrum. Our study illustrated that Lb2Cas12a could be harnessed as additional genome editing tool for the manipulation of human genome.