ArticleGenome biology2025
Predicting adenine base editing efficiencies in different cellular contexts by deep learning.
Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Rational selection of SpCas9 and variant-derived adenine base editors for human genome editing.Gene therapy · 2026Article
- Making base editing accessible: Evaluating computational workflows for ABE-mediated gene knockout.Molecular therapy. Nucleic acids · 2026Article
- Prime Editing, CRISPR-Cas9, and NanoCas Genome Editing for Cancer Treatment.Molecular biotechnology · 2026Review
- CRISPR-enhanced microalgae biosynthesis: a promising approach for future functional feed ingredients.Journal of animal science and biotechnology · 2026Review
- Deep learning models simultaneously trained on multiple datasets improve base-editing activity prediction.Nature communications · 2025Article
- A scalable proteogenomic framework for dissecting phospho-signaling pathways in primary immune cells.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
backgroundAdenine base editors (ABEs) enable the conversion of A•T to G•C base pairs. Since the sequence of the target locus influences base editing efficiency, efforts have been made to develop computational models that can predict base editing outcomes based on the targeted sequence. However, these models were trained on base editing datasets generated in cell lines and their predictive power for base editing in primary cells in vivo remains uncertain.
resultsIn this study, we conduct base editing screens using SpRY-ABEmax and SpRY-ABE8e to target 2,195 pathogenic mutations with a total of 12,000 guide RNAs in cell lines and in the murine liver. We observe strong correlations between in vitro datasets generated by ABE-mRNA electroporation into HEK293T cells and in vivo datasets generated by adeno-associated virus (AAV)- or lipid nanoparticle (LNP)-mediated nucleoside-modified mRNA delivery (Spearman R = 0.83-0.92). We subsequently develop BEDICT2.0, a deep learning model that predicts adenine base editing efficiencies with high accuracy in cell lines (R = 0.60-0.94) and in the liver (R = 0.62-0.81).
conclusionsIn conclusion, our work confirms that adenine base editing holds considerable potential for correcting a large fraction of pathogenic mutations. We also provide BEDICT2.0 - a robust computational model that helps identify sgRNA-ABE combinations capable of achieving high on-target editing with minimal bystander effects in both in vitro and in vivo settings.
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