ArticleNucleic acids research2022
Discovery of potent and versatile CRISPR-Cas9 inhibitors engineered for chemically controllable genome editing.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Technical limitations of CRISPR-Cas9 genome editing in bacteria: challenges and future directions.Archives of microbiology · 2026Review
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Structural basis for inhibition of SpyCas9 by the anti-CRISPR protein AcrIIA26.The Biochemical journal · 2026Article
- An anti-CRISPR targets the sgRNA to block Cas9 and guides the design of enhanced genome editors.Nature structural & molecular biology · 2026Article
- Multilayer regulation of CRISPR systems: integrating anti-CRISPR proteins, CRISPRi/a, and quorum sensing networks.Frontiers in cellular and infection microbiology · 2026Review
- A phage-encoded anti-CRISPR protein co-opts host enolase to prevent type III CRISPR immunity.Nature microbiology · 2025Article
- Engineering a CRISPR-associated IscB system for developing miniature genome-editing tools in human cells and mouse embryos.Nature communications · 2025Article
- Regulation of anti-CRISPR operons by structurally distinct families of Aca proteins.Communications biology · 2025Article
- Engineered probiotics: a new era in treating inflammatory bowel disease.Journal of translational medicine · 2025Review
- Analyzing the Challenges and Opportunities Associated With Harnessing New Antibiotics From the Fungal Microbiome.MicrobiologyOpen · 2025Review
- Identification of regulatory sequences in Aca11 and Aca13 for detection of anti-CRISPR and protein-protein interaction.Nucleic acids research · 2025Article
- A deep mutational scanning platform to characterize the fitness landscape of anti-CRISPR proteins.Nucleic acids research · 2024Article
- Versatile plant genome engineering using anti-CRISPR-Cas12a systems.Science China. Life sciences · 2024Article
- Inhibition mechanisms of CRISPR-Cas9 by AcrIIA25.1 and AcrIIA32.Science China. Life sciences · 2024Article
- AcrIIA28 is a metalloprotein that specifically inhibits targeted-DNA loading to SpyCas9 by binding to the REC3 domain.Nucleic acids research · 2024Article
- CRISPR/Cpf1-FOKI-induced gene editing inSynthetic and systems biotechnology · 2024Article
- Inhibitors of bacterial immune systems: discovery, mechanisms and applications.Nature reviews. Genetics · 2024Review
- Anti-CRISPR proteins trigger a burst of CRISPR-Cas9 expression that enhances phage defense.Cell reports · 2024Article
- 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
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-CRISPR (Acr) proteins are encoded by many mobile genetic elements (MGEs) such as phages and plasmids to combat CRISPR-Cas adaptive immune systems employed by prokaryotes, which provide powerful tools for CRISPR-Cas-based applications. Here, we discovered nine distinct type II-A anti-CRISPR (AcrIIA24-32) families from Streptococcus MGEs and found that most Acrs can potently inhibit type II-A Cas9 orthologs from Streptococcus (SpyCas9, St1Cas9 or St3Cas9) in bacterial and human cells. Among these Acrs, AcrIIA26, AcrIIA27, AcrIIA30 and AcrIIA31 are able to block Cas9 binding to DNA, while AcrIIA24 abrogates DNA cleavage by Cas9. Notably, AcrIIA25.1 and AcrIIA32.1 can inhibit both DNA binding and DNA cleavage activities of SpyCas9, exhibiting unique anti-CRISPR characteristics. Importantly, we developed several chemically inducible anti-CRISPR variants based on AcrIIA25.1 and AcrIIA32.1 by comprising hybrids of Acr protein and the 4-hydroxytamoxifen-responsive intein, which enabled post-translational control of CRISPR-Cas9-mediated genome editing in human cells. Taken together, our work expands the diversity of type II-A anti-CRISPR families and the toolbox of Acr proteins for the chemically inducible control of Cas9-based applications.
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