%0 Journal Article
%A Riesenberg, Stephan
%A Kanis, Philipp
%A Macak, Dominik
%A Wollny, Damian
%A Düsterhöft, Dorothee
%A Kowalewski, Johannes
%A Helmbrecht, Nelly
%A Maricic, Tomislav
%A Pääbo, Svante
%+ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T Efficient high-precision homology-directed repair-dependent genome editing by HDRobust : 
%G eng
%U https://hdl.handle.net/21.11116/0000-000D-78D4-D
%R 10.1038/s41592-023-01949-1
%7 2023-07-20
%D 2023
%* Review method: peer-reviewed
%X Homology-directed repair (HDR), a method for repair of DNA <br>double-stranded breaks can be leveraged for the precise introduction <br>of mutations supplied by synthetic DNA donors, but remains limited by <br>low efficiency and off-target effects. In this study, we report HDRobust, <br>a high-precision method that, via the combined transient inhibition of <br>nonhomologous end joining and microhomology-mediated end joining, <br>resulted in the induction of point mutations by HDR in up to 93% (median <br>60%, s.e.m. 3) of chromosomes in populations of cells. We found that, using <br>this method, insertions, deletions and rearrangements at the target site, as <br>well as unintended changes at other genomic sites, were largely abolished. <br>We validated this approach for 58 different target sites and showed that it <br>allows efficient correction of pathogenic mutations in cells derived from <br>patients suffering from anemia, sickle cell disease and thrombophilia.
%J Nature Methods
%V 20
%& 1388
%P 1388 - 1399
%@ 1548-70911548-7105