{"success":true,"partial":false,"results":[{"paperId":"6949331533423225193","primaryId":"pmcid:PMC12485731","ids":{"doi":["10.1101/2025.09.25.678665"],"pmcid":["PMC12485731"],"pmid":["41040263"]},"title":"Sensitive, direct detection of non-coding off-target base editor unwinding and editing in primary cells","abstract":"Using beCasKAS in primary human T-cells, we observe that mRNA-encoded ABE8e and PAMless ABE8e-SpRY base editors have distinct off-target profiles that can be mitigated by optimizing mRNA dose.","score":0.9684767772459986},{"paperId":"7661644968283019481","primaryId":"pmcid:PMC11552398","ids":{"doi":["10.1186/s13059-024-03434-0"],"pmcid":["PMC11552398"],"pmid":["39529170"]},"title":"Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells.","abstract":"Previous studies have reported that Cas9 cleavage induced frequent aneuploidy in primary human T cells, but whether cleavage-mediated editing of base editors would generate off-target structure variations remains unknown. In addition, off-target large deletions are detected in…","score":0.9644288107273639},{"paperId":"3622389691805862310","primaryId":"pmcid:PMC10188366","ids":{"doi":["10.1038/s41587-022-01533-6"],"pmcid":["PMC10188366"],"pmid":["36357719"]},"title":"Evolution of an adenine base editor into a small, efficient cytosine base editor with low off-target activity.","abstract":"Compared to commonly used CBEs, TadA-derived cytosine base editors (TadCBEs) offer similar or higher on-target activity, smaller size and substantially lower Cas-independent DNA and RNA off-target editing activity.","score":0.9013664124589823},{"paperId":"6659996386724007914","primaryId":"pmid:34478654","ids":{"doi":["10.1016/j.molcel.2021.07.035"],"pmid":["34478654"]},"title":"Conformational control of Cas9 by CRISPR hybrid RNA-DNA guides mitigates off-target activity in T cells.","abstract":"The off-target activity of the CRISPR-associated nuclease Cas9 is a potential concern for therapeutic genome editing applications. Although high-fidelity Cas9 variants have been engineered, they exhibit varying efficiencies and have residual off-target effects, limiting their…","score":0.8944949086405465},{"paperId":"2483673492666203694","primaryId":"pmcid:PMC8753564","ids":{"doi":["10.1016/j.ymthe.2021.10.026"],"pmcid":["PMC8753564"],"pmid":["34737067"]},"title":"Disruption of HIV-1 co-receptors CCR5 and CXCR4 in primary human T cells and hematopoietic stem and progenitor cells using base editing.","abstract":"Here, we applied base editors for individual and simultaneous disruption of both co-receptors in primary human CD4+ T cells. Using adenine base editors we eliminated the start codon in CCR5 in up to 95% of primary human CD4+ T cell and up to 88% of CD34+ hematopoietic stem and…","score":0.8740772351648677},{"paperId":"5058641532151454225","primaryId":"pmid:32284586","ids":{"doi":["10.1038/s41587-020-0491-6","10.1101/2020.03.13.990630"],"pmid":["32284586"]},"title":"Directed Evolution of Adenine Base Editors with Increased Activity and Therapeutic Application","abstract":"The foundational adenine base editors (e.g. ABE7.10) enable programmable C*G to T*A point mutations but editing efficiencies can be low at challenging loci in primary human cells. Here we further evolve ABE7.10 using a library of adenosine deaminase variants to create ABE8s. At…","score":0.8684702192881005},{"paperId":"1766123033087769924","primaryId":"pmcid:PMC8784854","ids":{"doi":["10.1002/cti2.1372"],"pmcid":["PMC8784854"],"pmid":["35106156"]},"title":"Genome-wide off-target analyses of CRISPR/Cas9-mediated T-cell receptor engineering in primary human T cells.","abstract":"Whole-genome sequencing was performed to analyse whether CRISPR/Cas9-mediated DNA double-strand break at the TCR locus is associated with off-target events in human primary T cells.","score":0.8596637505099167},{"paperId":"7792651039786783185","primaryId":"pmcid:PMC10172116","ids":{"doi":["10.1038/s41592-023-01840-z","10.1101/2022.10.29.514376"],"pmcid":["PMC10172116"],"pmid":["37024653"]},"title":"Improving the sensitivity of in vivo CRISPR off-target detection with DISCOVER-Seq+","abstract":"Discovery of off-target CRISPR-Cas genome editing activity in patient-derived cells and animal models is crucial for therapeutic applications, but currently exhibits low sensitivity. We demonstrate that inhibition of DNA-dependent protein kinase catalytic subunit (DNA-PKcs)…","score":0.8581489350995123},{"paperId":"9203881395391333608","primaryId":"pmcid:PMC12407836","ids":{"doi":["10.1101/2025.08.26.667396"],"pmcid":["PMC12407836"],"pmid":["40909481"]},"title":"An integrated enzymatic and computational pipeline for quantifying off-target base-editing","abstract":"DNA base editing is increasingly used for human genetic modification, but methods for monitoring off-target editing are nascent. Here we present a simple model-independent workflow for identifying sites of off-target base-editing in relevant cell types on a genome-wide level. We…","score":0.8405733129219832},{"paperId":"7472917013949357508","primaryId":"pmcid:PMC13188852","ids":{"doi":["10.1016/j.stem.2026.04.014"],"pmcid":["PMC13188852"],"pmid":["42134322"]},"title":"Genotoxicity profiling reveals distinct platform-and cell type-specific effects in therapeutic gene editing for genetic hyperinflammation.","abstract":"Base editors enable precise correction of point mutations without requiring DNA double-strand breaks, yet platform- and cell type-specific genotoxicities remain incompletely characterized. Here, we applied cytosine base editing (CBE) to disrupt a cryptic splice-site mutation in…","score":0.8371944748865756},{"paperId":"1709219101637597866","primaryId":"pmcid:PMC13463037","ids":{"doi":["10.1038/s41467-026-74623-7"],"pmcid":["PMC13463037"],"pmid":["42581041"]},"title":"UNCOVERseq enables sensitive and controlled gene editing off-target nomination across CRISPR-Cas modalities and systems.","abstract":"The rapid expansion of CRISPR-Cas gene editing enables new therapeutic strategies but complicates assessment of unintended editing risks due to emerging modalities and unclear analytical standards. We present UNCOVERseq (Unbiased Nomination of CRISPR Off-target Variants using…","score":0.7981867777396212},{"paperId":"2238794671122908609","primaryId":"pmcid:PMC6401248","ids":{"doi":["10.1038/s41587-018-0011-0"],"pmcid":["PMC6401248"],"pmid":["30742127"]},"title":"Engineered CRISPR-Cas12a variants with increased activities and improved targeting ranges for gene, epigenetic and base editing.","abstract":"Broad use of CRISPR-Cas12a (formerly Cpf1) nucleases1 has been hindered by the requirement for an extended TTTV protospacer adjacent motif (PAM)2. To address this limitation, we engineered an enhanced Acidaminococcus sp. Cas12a variant (enAsCas12a) that has a substantially…","score":0.795149548460553},{"paperId":"903631864113229013","primaryId":"pmcid:PMC6864045","ids":{"doi":["10.1038/s41467-019-13007-6","10.1101/482497"],"pmcid":["PMC6864045"],"pmid":["31745080"]},"title":"Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors","abstract":"Through systematic reagent and dose optimization, we demonstrate highly efficient multiplex base editing and consequent protein knockout in primary human T cells at loci relevant to the generation of allogeneic CAR-T cells including the T cell receptor constant (TRAC) locus,…","score":0.7718434978390747},{"paperId":"6782293538499203522","primaryId":"pmcid:PMC12107175","ids":{"doi":["10.1073/pnas.2427216122"],"pmcid":["PMC12107175"],"pmid":["40324075"]},"title":"Quadruple adenine base-edited allogeneic CAR T cells outperform CRISPR/Cas9 nuclease-engineered T cells.","abstract":"Genome-editing technologies have enabled the clinical development of allogeneic cellular therapies, yet the optimal gene-editing modality for multiplex editing of therapeutic T cell product manufacturing remains elusive. In this study, we conducted a comprehensive comparison of…","score":0.7662936430859597},{"paperId":"3482128144367177520","primaryId":"doi:10.1101/2021.04.05.438458","ids":{"doi":["10.1101/2021.04.05.438458"]},"title":"Global-scale CRISPR gene editor specificity profiling by ONE-seq identifies population-specific, variant off-target effects","abstract":"Defining off-target profiles of gene-editing nucleases and CRISPR base editors remains an important challenge for use of these technologies, therapeutic or otherwise. Existing methods can identify off-target sites induced by these gene editors on an individual genome but are not…","score":0.7651724826508884},{"paperId":"2248408133891109349","primaryId":"pmid:30833658","ids":{"doi":["10.1038/s41587-019-0050-1"],"pmid":["30833658"]},"title":"Genome-wide target specificity of CRISPR RNA-guided adenine base editors.","abstract":"Using targeted sequencing, we also show that use of preassembled adenine base editor ribonucleoproteins, modified guide RNAs5,8-11, and Sniper/Cas9 (ref. 12) reduces adenine base editor off-target activity in human cells.","score":0.759510916949111},{"paperId":"5174372009053172435","primaryId":"pmcid:PMC11754094","ids":{"doi":["10.1038/s41551-024-01277-5"],"pmcid":["PMC11754094"],"pmid":["39496933"]},"title":"Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases.","abstract":"When used to edit genomes, Cas9 nucleases produce targeted double-strand breaks in DNA. Subsequent DNA-repair pathways can induce large genomic deletions (larger than 100 bp), which constrains the applicability of genome editing. Here we show that Cas9-mediated double-strand…","score":0.751429334714939},{"paperId":"8027490479800411400","primaryId":"pmcid:PMC9263286","ids":{"doi":["10.1016/j.ymthe.2022.04.010"],"pmcid":["PMC9263286"],"pmid":["35443934"]},"title":"Eliminating predictable DNA off-target effects of cytosine base editor by using dual guiders including sgRNA and TALE.","abstract":"Predictable DNA off-target effect is one of the major safety concerns for the application of cytosine base editors (CBEs). To eliminate Cas9-dependent DNA off-target effects, we designed a novel effective CBE system with dual guiders by combining CRISPR with transcription…","score":0.7443591277196812},{"paperId":"1309132363644385250","primaryId":"pmid:42470099","ids":{"doi":["10.1016/j.ymthe.2026.07.033"],"pmid":["42470099"]},"title":"A singular base-editing platform for polyfunctional multiplex engineering of immune cells.","abstract":"Current methods to engineer antigen-specific receptors rely on randomly integrating vectors or double-strand-break-induced targeted integration, both of which pose safety risks. To implement an all-in-one tool for multiplex knockout (KO) and knockin (KI), we expand the use of…","score":0.7431680086124811},{"paperId":"1567418496726738663","primaryId":"pmid:34515826","ids":{"doi":["10.1007/s00294-021-01211-1"],"pmid":["34515826"]},"title":"Off-target effects of base editors: what we know and how we can reduce it.","abstract":"However, recent studies of non-specific activity of BEs revealed that some of them lead to the formation of a huge number of off-targets in both DNA and RNA, occurring due to the nature of the Cas9-fused proteins used.","score":0.740774899182154}]}