ArticleNucleic acids research2011
Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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.
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.
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Who cites it
68 citing papers in PubMed, 109 citations in OpenAlex.
- Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.Inflammation and regeneration · 2025Review
- Genome Editing Approaches Using Zinc Finger Nucleases (ZFNs) for the Treatment of Motor Neuron Diseases.Current pharmaceutical biotechnology · 2025Review
- Principles of Zebrafish Nephron Segment Development.Journal of developmental biology · 2023Review
- Advancement in the Breeding, Biotechnological and Genomic Tools towards Development of Durable Genetic Resistance against the Rice Blast Disease.Plants (Basel, Switzerland) · 2022Review
- Genome engineering and disease modelingWorld journal of stem cells · 2021Review
- Tools for experimental and computational analyses of off-target editing by programmable nucleases.Nature protocols · 2021Review
- The Off-Targets of Clustered Regularly Interspaced Short Palindromic Repeats Gene Editing.Frontiers in cell and developmental biology · 2021Review
- Divalent cations promote TALE DNA-binding specificity.Nucleic acids research · 2020Article
- Molecular mechanisms, off-target activities, and clinical potentials of genome editing systems.Clinical and translational medicine · 2020Review
- RNA-Seq Analysis of an Antisense Sequence Optimized for Exon Skipping in Duchenne Patients Reveals No Off-Target Effect.Molecular therapy. Nucleic acids · 2018Article
- Applications of Alternative Nucleases in the Age of CRISPR/Cas9.International journal of molecular sciences · 2017Review
- Targeted mutagenesis: A sniper-like diversity generator in microbial engineering.Synthetic and systems biotechnology · 2017Review
- Review
- A genome editing primer for the hematologist.Blood · 2016Review
- Editing of the Luteinizing Hormone Gene to Sterilize Channel Catfish, Ictalurus punctatus, Using a Modified Zinc Finger Nuclease Technology with Electroporation.Marine biotechnology (New York, N.Y.) · 2016Article
- Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Multidimensional Genome-wide Analyses Show Accurate FVIII Integration by ZFN in Primary Human Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Generation of TALE nickase-mediated gene-targeted cows expressing human serum albumin in mammary glands.Scientific reports · 2016Article
- Mechanisms of gene targeting in higher eukaryotes.Cellular and molecular life sciences : CMLS · 2016Review
- DNA-binding-domain fusions enhance the targeting range and precision of Cas9.Nature methods · 2015Article
8 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Zinc finger nucleases (ZFNs) facilitate tailor-made genomic modifications in vivo through the creation of targeted double-stranded breaks. They have been employed to modify the genomes of plants and animals, and cell-based therapies utilizing ZFNs are undergoing clinical trials. However, many ZFNs display dose-dependent toxicity presumably due to the generation of undesired double-stranded breaks at off-target sites. To evaluate the parameters influencing the functional specificity of ZFNs, we compared the in vivo activity of ZFN variants targeting the zebrafish kdrl locus, which display both high on-target activity and dose-dependent toxicity. We evaluated their functional specificity by assessing lesion frequency at 141 potential off-target sites using Illumina sequencing. Only a minority of these off-target sites accumulated lesions, where the thermodynamics of zinc finger-DNA recognition appear to be a defining feature of active sites. Surprisingly, we observed that both the specificity of the incorporated zinc fingers and the choice of the engineered nuclease domain could independently influence the fidelity of these ZFNs. The results of this study have implications for the assessment of likely off-target sites within a genome and point to both zinc finger-dependent and -independent characteristics that can be tailored to create ZFNs with greater precision.
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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.