ArticleScience advances2020
Coupling Cas9 to artificial inhibitory domains enhances CRISPR-Cas9 target specificity.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed.
- 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
- Identification of regulatory sequences in Aca11 and Aca13 for detection of anti-CRISPR and protein-protein interaction.Nucleic acids research · 2025Article
- Modulation of CRISPR-Cas9 Cleavage with an Oligo-Ribonucleoprotein Design.Chembiochem : a European journal of chemical biology · 2025Article
- A deep mutational scanning platform to characterize the fitness landscape of anti-CRISPR proteins.Nucleic acids research · 2024Article
- Insight into the natural regulatory mechanisms and clinical applications of the CRISPR-Cas system.Heliyon · 2024Review
- Computationally guided high-throughput engineering of an anti-CRISPR protein for precise genome editing in human cells.Cell reports methods · 2024Article
- High-resolution and programmable RNA-IN and RNA-OUT genetic circuit in living mammalian cells.Nature communications · 2024Article
- Structural basis of negative regulation of CRISPR-Cas7-11 by TPR-CHAT.Signal transduction and targeted therapy · 2024Article
- Selection of extended CRISPR RNAs with enhanced targeting and specificity.Communications biology · 2024Article
- Current Updates of CRISPR/Cas System and Anti-CRISPR Proteins: Innovative Applications to Improve the Genome Editing Strategies.International journal of nanomedicine · 2024Review
- Rapid characterization of anti-CRISPR proteins and optogenetically engineered variants using a versatile plasmid interference system.Nucleic acids research · 2023Article
- CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023Review
- Search for Origins of Anti-CRISPR Proteins by Structure Comparison.The CRISPR journal · 2023Article
- Mechanisms regulating the CRISPR-Cas systems.Frontiers in microbiology · 2023Review
- Application of CRISPR-Cas system in the diagnosis and therapy of ESKAPE infections.Frontiers in cellular and infection microbiology · 2023Review
- Beyond the promise: evaluating and mitigating off-target effects in CRISPR gene editing for safer therapeutics.Frontiers in bioengineering and biotechnology · 2023Review
- RNA-Responsive gRNAs for Controlling CRISPR Activity: Current Advances, Future Directions, and Potential Applications.The CRISPR journal · 2022Review
- Small Molecules for Enhancing the Precision and Safety of Genome Editing.Molecules (Basel, Switzerland) · 2022Review
- CRISPR-Cas system: from diagnostic tool to potential antiviral treatment.Applied microbiology and biotechnology · 2022Review
- Rational guide RNA engineering for small-molecule control of CRISPR/Cas9 and gene editing.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The limited target specificity of CRISPR-Cas nucleases poses a challenge with respect to their application in research and therapy. Here, we present a simple and original strategy to enhance the specificity of CRISPR-Cas9 genome editing by coupling Cas9 to artificial inhibitory domains. Applying a combination of mathematical modeling and experiments, we first determined how CRISPR-Cas9 activity profiles relate to Cas9 specificity. We then used artificially weakened anti-CRISPR (Acr) proteins either coexpressed with or directly fused to Cas9 to fine-tune its activity toward selected levels, thereby achieving an effective kinetic insulation of ON- and OFF-target editing events. We demonstrate highly specific genome editing in mammalian cells using diverse single-guide RNAs prone to potent OFF-targeting. Last, we show that our strategy is compatible with different modes of delivery, including transient transfection and adeno-associated viral vectors. Together, we provide a highly versatile approach to reduce CRISPR-Cas OFF-target effects via kinetic insulation.
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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.