ArticleScience advances2017
Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity.
Article in Science advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 483 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
483 citing papers in PubMed, 1 synthesis or guideline pooled it, 767 citations in OpenAlex.
- CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Pooled it
- Base Editing: Mechanisms and Therapeutic Applications.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Translating base editors: a decade of progress from the bench to the clinic.Nature reviews. Drug discovery · 2026Review
- Validation of a Modular Base Editing Strategy, Free-BE, inPlant direct · 2026Article
- Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Base editing for precision therapeutics.Cell genomics · 2026Review
- In vivo base editing of Asgr1 reduces blood lipids in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- High-diversity base mutagenesis via simultaneous adenine, cytosine and guanine editing.Nature communications · 2026Article
- Replication-coupled dual-deaminase mutagenesis (RCDM) enables continuous genomic evolution in Bacillus subtilis.Microbial cell factories · 2026Article
- Structure-guided engineering of AI-derived adenine base editors for nuclear and mitochondrial DNA editing.Nucleic acids research · 2026Article
- Efficient in vivo cytosine base editing using virus-like particles with uracil DNA glycosylase inhibition.Nature biotechnology · 2026Article
- Overcoming the challenges of genome-editing essential genes.STAR protocols · 2026Review
- Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes.Nature biotechnology · 2026Article
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Base editing-derived models of human WDR34 and WDR60 disease alleles replicate retrograde intraflagellar transport (IFT) and hedgehog signaling defects.Communications biology · 2026Article
- Engineered transformer base editor with unconstrained PAM requirements.Molecular therapy. Nucleic acids · 2026Article
- Machine learning-driven optimization of specific, compact, and efficient base editors via single-round diversification.Nucleic acids research · 2026Article
- Base Editors for Engineering Industrial Microorganisms: Types, Applications, and Future Perspectives.Biotechnology journal · 2026Review
- Advances in multiplex precision genome editing in eukaryotic and prokaryotic systems.Current opinion in biotechnology · 2026Review
- Gene Editing Strategies for Duchenne Muscular Dystrophy: From Molecular Mechanisms to Clinical Translation.Cells · 2026Review
423 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
We recently developed base editing, the programmable conversion of target C:G base pairs to T:A without inducing double-stranded DNA breaks (DSBs) or requiring homology-directed repair using engineered fusions of Cas9 variants and cytidine deaminases. Over the past year, the third-generation base editor (BE3) and related technologies have been successfully used by many researchers in a wide range of organisms. The product distribution of base editing-the frequency with which the target C:G is converted to mixtures of undesired by-products, along with the desired T:A product-varies in a target site-dependent manner. We characterize determinants of base editing outcomes in human cells and establish that the formation of undesired products is dependent on uracil N-glycosylase (UNG) and is more likely to occur at target sites containing only a single C within the base editing activity window. We engineered CDA1-BE3 and AID-BE3, which use cytidine deaminase homologs that increase base editing efficiency for some sequences. On the basis of these observations, we engineered fourth-generation base editors (BE4 and SaBE4) that increase the efficiency of C:G to T:A base editing by approximately 50%, while halving the frequency of undesired by-products compared to BE3. Fusing BE3, BE4, SaBE3, or SaBE4 to Gam, a bacteriophage Mu protein that binds DSBs greatly reduces indel formation during base editing, in most cases to below 1.5%, and further improves product purity. BE4, SaBE4, BE4-Gam, and SaBE4-Gam represent the state of the art in C:G-to-T:A base editing, and we recommend their use in future efforts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.