ReviewCell systems2017
Lessons from Enzyme Kinetics Reveal Specificity Principles for RNA-Guided Nucleases in RNA Interference and CRISPR-Based Genome Editing.
Review in Cell systems, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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.
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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.
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Who cites it
53 citing papers in PubMed.
- Rho (bioRxiv : the preprint server for biology · 2026Article
- Cas-regulation-targeting chimera enables selective and tunable control of CRISPR/Cas12a.Nucleic acids research · 2026Article
- Operating CRISPR/Cas12a in a complex nucleic acid sequence background.Nucleic acids research · 2026Article
- How Binding Affinity and Binding Specificity Map to Sequence Space.Journal of molecular evolution · 2026Article
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- The virulence regulator CovR boosts CRISPR-Cas9 immunity in Group B Streptococcus.Nature communications · 2025Article
- A rational engineering strategy for structural dynamics modulation enables target specificity enhancement of the Cas9 nuclease.Nucleic acids research · 2025Article
- High Bendability of Short RNA-DNA Hybrid Duplex Revealed by Single-Molecule Cyclization and Molecular Dynamics Simulations.Biomolecules · 2025Article
- Rational Design of Enhanced Nme2Cas9 and Nme2bioRxiv : the preprint server for biology · 2024Article
- Iterative crRNA design and a PAM-free strategy enabled an ultra-specific RPA-CRISPR/Cas12a detection platform.Communications biology · 2024Article
- Engineering Cas9: next generation of genomic editors.Applied microbiology and biotechnology · 2024Review
- New design strategies for ultra-specific CRISPR-Cas13a-based RNA detection with single-nucleotide mismatch sensitivity.Nucleic acids research · 2024Article
- Characterization of the AcrIIC1 anti‒CRISPR protein for Cas9‒based genome engineering in E. coli.Communications biology · 2023Article
- The energy landscape for R-loop formation by the CRISPR-Cas Cascade complex.Nature structural & molecular biology · 2023Article
- Improving the on-target activity of high-fidelity Cas9 editors by combining rational design and random mutagenesis.Applied microbiology and biotechnology · 2023Article
- CRISPR-Cas9 recognition of enzymatically synthesized base-modified nucleic acids.Nucleic acids research · 2023Article
- A quantitative model for the dynamics of target recognition and off-target rejection by the CRISPR-Cas Cascade complex.Nature communications · 2022Article
- Modulating CRISPR-Cas Genome Editing Using Guide-Complementary DNA Oligonucleotides.The CRISPR journal · 2022Article
- Microfluidic tool for rapid functional characterization of CRISPR complexes.New biotechnology · 2022Article
- A kinetic model predicts SpCas9 activity, improves off-target classification, and reveals the physical basis of targeting fidelity.Nature communications · 2022Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
RNA-guided nucleases (RGNs) provide sequence-specific gene regulation through base-pairing interactions between a small RNA guide and target RNA or DNA. RGN systems, which include CRISPR-Cas9 and RNA interference (RNAi), hold tremendous promise as programmable tools for engineering and therapeutic purposes. However, pervasive targeting of sequences that closely resemble the intended target has remained a major challenge, limiting the reliability and interpretation of RGN activity and the range of possible applications. Efforts to reduce off-target activity and enhance RGN specificity have led to a collection of empirically derived rules, which often paradoxically include decreased binding affinity of the RNA-guided nuclease to its target. We consider the kinetics of these reactions and show that basic kinetic properties can explain the specificities observed in the literature and the changes in these specificities in engineered systems. The kinetic models described provide a foundation for understanding RGN targeting and a necessary conceptual framework for their rational engineering.
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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.