@article {1574705,
	title = {Enabling large-scale genome editing at repetitive elements by reducing DNA nicking},
	journal = {Nucleic Acids Res},
	volume = {48},
	number = {9},
	year = {2020},
	month = {2020 05 21},
	pages = {5183-5195},
	abstract = {To extend the frontier of genome editing and enable editing of repetitive elements of mammalian genomes, we made use of a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks and single-strand breaks. We used a set of gRNAs targeting repetitive elements-ranging in target copy number from about 32 to 161 000 per cell. dBEs enabled survival after large-scale base editing, allowing targeted mutations at up to \~{}13 200 and \~{}12 200 loci in 293T and human induced pluripotent stem cells (hiPSCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering.},
	keywords = {Cell Survival, CRISPR-Associated Proteins, CRISPR-Cas Systems, Endodeoxyribonucleases, Gene Editing, HEK293 Cells, Humans, Induced Pluripotent Stem Cells, Mutation, Retroelements, RNA},
	issn = {1362-4962},
	doi = {10.1093/nar/gkaa239},
	author = {Smith, Cory J and Castanon, Oscar and Said, Khaled and Volf, Verena and Khoshakhlagh, Parastoo and Hornick, Amanda and Ferreira, Raphael and Wu, Chun-Ting and G{\"u}ell, Marc and Garg, Shilpa and Ng, Alex H M and Myllykallio, Hannu and Church, George M}
}
