ArticleCell reports methods2024
Computationally guided high-throughput engineering of an anti-CRISPR protein for precise genome editing in human cells.
Article in Cell reports methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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.
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Who cites it
5 citing papers in PubMed.
- Artificial intelligence in biomarker discovery for diseases: diagnostic and therapeutic prospects.Signal transduction and targeted therapy · 2026Review
- Advanced Strategies in Phage Research: Innovations, Applications, and Challenges.Microorganisms · 2025Review
- Protective antigen-mediated delivery of an anti-CRISPR protein for precision genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Recommendations for robust and reproducible research on ferroptosis.Nature reviews. Molecular cell biology · 2025Review
- Mechanism of Cas9 inhibition by AcrIIA11.Nucleic acids research · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The application of CRISPR-Cas systems to genome editing has revolutionized experimental biology and is an emerging gene and cell therapy modality. CRISPR-Cas systems target off-target regions within the human genome, which is a challenge that must be addressed. Phages have evolved anti-CRISPR proteins (Acrs) to evade CRISPR-Cas-based immunity. Here, we engineer an Acr (AcrIIA4) to increase the precision of CRISPR-Cas-based genome targeting. We developed an approach that leveraged (1) computational guidance, (2) deep mutational scanning, and (3) highly parallel DNA repair measurements within human cells. In a single experiment, ∼10,000 Acr variants were tested. Variants that improved editing precision were tested in additional validation experiments that revealed robust enhancement of gene editing precision and synergy with a high-fidelity version of Cas9. This scalable high-throughput screening framework is a promising methodology to engineer Acrs to increase gene editing precision, which could be used to improve the safety of gene editing-based therapeutics.
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Registered trials
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