ArticleNature chemical biology2018
Partial DNA-guided Cas9 enables genome editing with reduced off-target activity.
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed.
- 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
- Improved specificity and efficiency of in vivo adenine base editing therapies with hybrid guide RNAs.Nature biomedical engineering · 2026Article
- CRISPR RNA architecture steers Cas9 catalysis and fidelity via a guide repeat clasp motif.Nucleic acids research · 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
- Guide DNA - not RNA - expands the CRISPR toolkit.Nature biotechnology · 2026Article
- Application of extracellular vesicles in the CRISPR-based diagnosis and treatment: possibilities and challenges.Journal of biological engineering · 2026Review
- Abasic CRISPR RNAs inherently harness fidelity of SpCas9 for genome editing.Nature chemical biology · 2026Article
- CRISPR screening redefines therapeutic target identification and drug discovery with precision and scalability.Journal of pharmaceutical analysis · 2026Review
- Chemical control of 2'-hydroxyl-dependent Cas9 target engagement enables CRISPR RNA ribose replacement.bioRxiv : the preprint server for biology · 2026Article
- Synthesis of long and functionally active RNAs facilitated by acetal levulinic ester chemistry.Nucleic acids research · 2026Article
- Bio-orthogonal chemistry-based strategy to Turn-OFF CRISPR-Cas9 activity in solution and live cells.NAR molecular medicine · 2026Article
- Coumarin-Based Photolabile Solid Support Facilitates Nonchromatographic Purification of RNA Oligonucleotides.The Journal of organic chemistry · 2025Article
- ARROW: Allele-Specific Recombined gRNA Design for Reduced Off-Target with Enhanced Specificity.Bioengineering (Basel, Switzerland) · 2025Article
- RNA chemistry and therapeutics.Nature reviews. Drug discovery · 2025Review
- Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.Journal of hematology & oncology · 2025Review
- CRISPR-Cas Systems: A Functional Perspective and Innovations.International journal of molecular sciences · 2025Review
- Chemical engineering of CRISPR-Cas systems for therapeutic application.Nature reviews. Drug discovery · 2025Review
- Modulation of CRISPR-Cas9 Cleavage with an Oligo-Ribonucleoprotein Design.Chembiochem : a European journal of chemical biology · 2025Article
- Article
53 more citing papers are in PubMed but not listed here.
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14 authors.
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Abstract
CRISPR-Cas9 is a versatile RNA-guided genome editing tool. Here we demonstrate that partial replacement of RNA nucleotides with DNA nucleotides in CRISPR RNA (crRNA) enables efficient gene editing in human cells. This strategy of partial DNA replacement retains on-target activity when used with both crRNA and sgRNA, as well as with multiple guide sequences. Partial DNA replacement also works for crRNA of Cpf1, another CRISPR system. We find that partial DNA replacement in the guide sequence significantly reduces off-target genome editing through focused analysis of off-target cleavage, measurement of mismatch tolerance and genome-wide profiling of off-target sites. Using the structure of the Cas9-sgRNA complex as a guide, the majority of the 3' end of crRNA can be replaced with DNA nucleotide, and the 5 - and 3'-DNA-replaced crRNA enables efficient genome editing. Cas9 guided by a DNA-RNA chimera may provide a generalized strategy to reduce both the cost and the off-target genome editing in human cells.
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