ArticleNature biotechnology2018
A highly specific SpCas9 variant is identified by in vivo screening in yeast.
Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 285 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
285 citing papers in PubMed, 1 synthesis or guideline pooled it.
- CRISPR/Cas-Based Modifications for Therapeutic Applications: A Review.Molecular biotechnology · 2022Pooled it
- Trial
- Non-Viral CRISPR carriers: transient delivery with lasting effects.Drug delivery · 2026Review
- CRISPR-Cas9 in Cancer Therapy: Overcoming Delivery Barriers and Off-Target Effects for Clinical Translation.Health science reports · 2026Article
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- Rational selection of SpCas9 and variant-derived adenine base editors for human genome editing.Gene therapy · 2026Article
- A dynamically frustrated allosteric checkpoint consistent with conformational proofreading in CRISPR-Cas9.Nucleic acids research · 2026Article
- CRISPR-Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus.Molecular biology reports · 2026Review
- Identification and structure determination of a type III-Bv CRISPR complex that post-translationally modifies an associated toxin.Structure (London, England : 1993) · 2026Article
- Chemical and Structural Engineering of Guide RNAs for Precision Genome Editing: From Design Principles to Clinical Applications.Chemical biology & drug design · 2026Review
- The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.Pediatric research · 2026Review
- High-throughput evaluation of in vitro CRISPR activities enables optimized large-scale multiplex enrichment of rare variants.Nature biomedical engineering · 2026Article
- Wheat's Up with CRISPR-Cas-Current Advances, Obstacles and Perspectives.International journal of molecular sciences · 2026Review
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- Inducible CRISPR/Cas systems in precision oncology: Current applications and future perspectives.Clinical and translational medicine · 2026Review
- High-fidelity genome and prime editing enabled by the AI-designed openCRISPR-1.Genome medicine · 2026Article
- Gene Editing Strategies for Duchenne Muscular Dystrophy: From Molecular Mechanisms to Clinical Translation.Cells · 2026Review
- Multilevel characterization of genome editor nuclease activity with BreakTag.Nature protocols · 2026Review
- Application of extracellular vesicles in the CRISPR-based diagnosis and treatment: possibilities and challenges.Journal of biological engineering · 2026Review
- Cas9-Embedding Hyperactive TadA8e Confers Efficient and Highly Specific A-To-G Base Editing in Rice.Plant biotechnology journal · 2026Article
225 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
12 authors.
Funding
Abstract
Despite the utility of CRISPR-Cas9 nucleases for genome editing, the potential for off-target activity limits their application, especially for therapeutic purposes. We developed a yeast-based assay to identify optimized Streptococcus pyogenes Cas9 (SpCas9) variants that enables simultaneous evaluation of on- and off-target activity. We screened a library of SpCas9 variants carrying random mutations in the REC3 domain and identified mutations that increased editing accuracy while maintaining editing efficiency. We combined four beneficial mutations to generate evoCas9, a variant that has fidelity exceeding both wild-type (79-fold improvement) and rationally designed Cas9 variants (fourfold average improvement), while maintaining near wild-type on-target editing efficiency (90% median residual activity). Evaluating evoCas9 on endogenous genomic loci, we demonstrated a substantially improved specificity and observed no off-target sites for four of the eight single guide RNAs (sgRNAs) tested. Finally, we showed that following long-term expression (40 d), evoCas9 strongly limited the nonspecific cleavage of a difficult-to-discriminate off-target site and fully abrogated the cleavage of two additional off-target sites.
Indexed as
Identifiers
What OpenQuestion holds
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.