ArticleNature biotechnology2015
Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition.
Article in Nature biotechnology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 381 papers.
What it found
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The trial behind it
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Who cites it
381 citing papers in PubMed.
- Protocol for quantification of AAV-CRISPR-mediated hepatic gene editing in mice.STAR protocols · 2026Article
- CRISPR-Cas13-based amplification-free detection of three quarantine-significant sugarcane viruses.Plant cell reports · 2026Article
- Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- In vivo base editing of Asgr1 reduces blood lipids in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- In vivo CRISPR base editing for treatment of Huntington's disease.Nature biomedical engineering · 2026Article
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- dSaCas9 enables enhanced transcriptional activation in Nicotiana benthamiana compared to its dSpCas9 ortholog.BMC plant biology · 2026Article
- Therapeutic adenine base editor with minimized off-target effects.Protein & cell · 2026Article
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Fully computational design of PAM-relaxedeLife · 2026Article
- Treatment of a severe vascular disease using a bespoke CRISPR-Cas9 base editor in mice.Nature biomedical engineering · 2026Article
- Engineering a compact high-fidelity Staphylococcus aureus Cas9 variant with broader targeting range and mechanistic insights into its activation.Nature communications · 2026Article
- Fully computational design of PAM-relaxedbioRxiv : the preprint server for biology · 2026Article
- Regulated transformation system (RTS): sddi-mediated programmable shut-off and mode switching of base editors.Nucleic acids research · 2026Article
- Therapeutic base editing alleviates restrictive cardiomyopathy.Cell reports. Medicine · 2026Article
- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 2026Review
- Haplotype editing with CRISPR-Cas9 as a therapeutic approach for dominant-negative missense mutations in NEFL.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Nature Inspired Delivery Vehicles for CRISPR-Based Genome Editing.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
321 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
CRISPR-Cas9 nucleases target specific DNA sequences using a guide RNA but also require recognition of a protospacer adjacent motif (PAM) by the Cas9 protein. Although longer PAMs can potentially improve the specificity of genome editing, they limit the range of sequences that Cas9 orthologs can target. One potential strategy to relieve this restriction is to relax the PAM recognition specificity of Cas9. Here we used molecular evolution to modify the NNGRRT PAM of Staphylococcus aureus Cas9 (SaCas9). One variant we identified, referred to as KKH SaCas9, showed robust genome editing activities at endogenous human target sites with NNNRRT PAMs, thereby increasing SaCas9 targeting range by two- to fourfold. Using GUIDE-seq, we show that wild-type and KKH SaCas9 induce comparable numbers of off-target effects in human cells. Our strategy for evolving PAM specificity does not require structural information and therefore should be applicable to a wide range of Cas9 orthologs.
Identifiers
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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.