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PMID:30190307

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Citation

Watters, KE, Fellmann, C, Bai, HB, Ren, SM and Doudna, JA (2018) Systematic discovery of natural CRISPR-Cas12a inhibitors. Science 362:236-239

Abstract

Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. Although bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9, Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for CRISPR-Cas12a. Here we use a comprehensive bioinformatic and experimental screening approach to identify three different inhibitors that block or diminish CRISPR-Cas12a-mediated genome editing in human cells. We also find a widespread connection between CRISPR self-targeting and inhibitor prevalence in prokaryotic genomes, suggesting a straightforward path to the discovery of many more anti-CRISPRs from the microbial world.

Links

PubMed PMC6185749 Online version:10.1126/science.aau5138

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

9GAMM:A0A0U2BNN7

GO:0099048: CRISPR-cas system

IDA: Inferred from Direct Assay:

P

Fig. 3 demonstrates that acrVA1 from Moraxella bovoculi inhibits the effect of DNA modification by MbCas 12a, LbCas 12, and AsCas12 proteins. Note: NTR #16423 was submitted, waiting for reply. These proteins are negatively regulating this process.

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Notes

See also

References

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