ArticleNature biotechnology2025
Development of multiplexed orthogonal base editor (MOBE) systems.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Adenine base editor for knockout of proteins: A practical guide from design to analysis with updated MultiEditRbatch.Molecular therapy. Nucleic acids · 2026Article
- Multiplexed, precise genome engineering in monocots with twin prime editing systems.Nature biotechnology · 2026Article
- Advances in multiplex precision genome editing in eukaryotic and prokaryotic systems.Current opinion in biotechnology · 2026Review
- Boosting prime editing with engineered non-canonical pegRNAs.Nature biomedical engineering · 2026Article
- Regulated transformation system (RTS): sddi-mediated programmable shut-off and mode switching of base editors.Nucleic acids research · 2026Article
- Precise, minimally evolved adenine base editors generated through mutation reversion analysis.Nature biotechnology · 2026Article
- Highly efficient expression of DNA-peptide conjugates in growth-arrested cells.Nature communications · 2026Article
- Development and Future Prospects of Bamboo Gene Science.International journal of molecular sciences · 2025Review
- Toward optimizing diversifying base editors for high-throughput mutational scanning studies.Nucleic acids research · 2025Article
- Charting the development and engineering of CRISPR base editors: lessons and inspirations.Cell chemical biology · 2025Review
- Development of multiplexed orthogonal base editor (MOBE) systems.Nature biotechnology · 2025Article
- Genome editing with programmable base editors in human cells.Methods in enzymology · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Base editors (BEs) enable efficient, programmable installation of point mutations while avoiding the use of double-strand breaks. Simultaneous application of two or more different BEs, such as an adenine BE (which converts A·T base pairs to G·C) and a cytosine BE (which converts C·G base pairs to T·A), is not feasible because guide RNA crosstalk results in non-orthogonal editing, with all BEs modifying all target loci. Here we engineer both adenine BEs and cytosine BEs that can be orthogonally multiplexed by using RNA aptamer-coat protein systems to recruit the DNA-modifying enzymes directly to the guide RNAs. We generate four multiplexed orthogonal BE systems that enable rates of precise co-occurring edits of up to 7.1% in the same DNA strand without enrichment or selection strategies. The addition of a fluorescent enrichment strategy increases co-occurring edit rates up to 24.8% in human cells. These systems are compatible with expanded protospacer adjacent motif and high-fidelity Cas9 variants, function well in multiple cell types, have equivalent or reduced off-target propensities compared with their parental systems and can model disease-relevant point mutation combinations.
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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.