{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(1)"],"submitter":["Fu J"],"pubmed_abstract":["Adenine base editors (ABE) are genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion. However, the low activity of ABE at certain sites remains a major bottleneck that precludes efficacious applications. Here, to address it, we develop a directional screening system in human cells to evolve the deaminase component of the ABE, and identify three high-activity NG-ABEmax variants: NG-ABEmax-SGK (R101S/D139G/E140K), NG-ABEmax-R (Q154R) and NG-ABEmax-K (N127K). With further engineering, we create a consolidated variant [NG-ABEmax-KR (N127K/Q154R)] which exhibit superior editing activity both in human cells and in mouse disease models, compared to the original NG-ABEmax. We also find that NG-ABEmax-KR efficiently introduce natural mutations in gamma globin gene promoters with more than four-fold increase in editing activity. This work provides a broadly applicable, rapidly deployable platform to directionally screen and evolve user-specified traits in base editors that extend beyond augmented editing activity."],"journal":["Nature communications"],"pagination":["5897"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8501064"],"repository":["biostudies-literature"],"pubmed_title":["Human cell based directed evolution of adenine base editors with improved efficiency."],"pmcid":["PMC8501064"],"pubmed_authors":["Liu X","Lv J","Yin X","Tu T","Li J","Zhang J","Lv X","Gu F","Fu J","Qu J","Li Q","Song Z"],"additional_accession":[]},"is_claimable":false,"name":"Human cell based directed evolution of adenine base editors with improved efficiency.","description":"Adenine base editors (ABE) are genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion. However, the low activity of ABE at certain sites remains a major bottleneck that precludes efficacious applications. Here, to address it, we develop a directional screening system in human cells to evolve the deaminase component of the ABE, and identify three high-activity NG-ABEmax variants: NG-ABEmax-SGK (R101S/D139G/E140K), NG-ABEmax-R (Q154R) and NG-ABEmax-K (N127K). With further engineering, we create a consolidated variant [NG-ABEmax-KR (N127K/Q154R)] which exhibit superior editing activity both in human cells and in mouse disease models, compared to the original NG-ABEmax. We also find that NG-ABEmax-KR efficiently introduce natural mutations in gamma globin gene promoters with more than four-fold increase in editing activity. This work provides a broadly applicable, rapidly deployable platform to directionally screen and evolve user-specified traits in base editors that extend beyond augmented editing activity.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2025-04-18T13:35:07.616Z","creation":"2025-04-06T23:23:39.577Z"},"accession":"S-EPMC8501064","cross_references":{"pubmed":["34625552"],"doi":["10.1038/s41467-021-26211-0"]}}