ArticleScientific reports2023
The PROTECTOR strategy employs dCas orthologs to sterically shield off-target sites from CRISPR/Cas activity.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Gene editing of NCF1 loci is associated with homologous recombination and chromosomal rearrangements.Communications biology · 2024Article
- Selection of extended CRISPR RNAs with enhanced targeting and specificity.Communications biology · 2024Article
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Authors and funding
2 authors.
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Abstract
Off-target mutagenesis of CRISPR/Cas systems must be solved to facilitate safe gene therapy. Here, we report a novel approach, termed "PROTECTOR", to shield known off-target sites by directing the binding of an orthologous nuclease-dead Cas protein to the off-target site to sterically interfere with Cas activity. We show that this method reduces off-target mutation rates of two well-studied guide RNAs without compromising on-target activity and that it can be used in combination with high-fidelity Cas enzymes to further reduce off-target editing. This expands the suite of off-target mitigation strategies and offers an ability to protect off-target sites even when their sequences are fully identical to target sites.
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