ArticlePLoS genetics2009
Attenuation of zinc finger nuclease toxicity by small-molecule regulation of protein levels.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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
79 citing papers in PubMed, 138 citations in OpenAlex.
- Recent Advancements for Enhanced Biocatalyst and Biotransformation.Molecular biotechnology · 2026Review
- Genome Editing Approaches Using Zinc Finger Nucleases (ZFNs) for the Treatment of Motor Neuron Diseases.Current pharmaceutical biotechnology · 2025Review
- Article
- Epigenetic Editing in Prostate Cancer: Challenges and Opportunities.Epigenetics · 2022Review
- High-Throughput Imaging of CRISPR- and Recombinant Adeno-Associated Virus-Induced DNA Damage Response in Human Hematopoietic Stem and Progenitor Cells.The CRISPR journal · 2022Article
- Advance trends in targeting homology-directed repair for accurate gene editing: An inclusive review of small molecules and modified CRISPR-Cas9 systems.BioImpacts : BI · 2022Review
- CRISPR/Cas9 treatment causes extended TP53-dependent cell cycle arrest in human cells.Nucleic acids research · 2020Article
- Systematic Identification of Regulators of Oxidative Stress Reveals Non-canonical Roles for Peroxisomal Import and the Pentose Phosphate Pathway.Cell reports · 2020Article
- Chimerization Enables Gene Synthesis and Lentiviral Delivery of Customizable TALE-Based Effectors.International journal of molecular sciences · 2020Article
- Genome Editing with mRNA Encoding ZFN, TALEN, and Cas9.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Review
- Gene correction for SCID-X1 in long-term hematopoietic stem cells.Nature communications · 2019Article
- HDAd5/35Molecular therapy. Methods & clinical development · 2018Article
- Cell-penetrating peptides and their utility in genome function modifications (Review).International journal of molecular medicine · 2017Review
- Therapeutic Gene Editing Safety and Specificity.Hematology/oncology clinics of North America · 2017Review
- Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens.Nature communications · 2017Article
- Programmable Genome Editing Tools and their Regulation for Efficient Genome Engineering.Computational and structural biotechnology journal · 2017Review
- Combining Engineered Nucleases with Adeno-associated Viral Vectors for Therapeutic Gene Editing.Advances in experimental medicine and biology · 2017Review
- Genome-Editing Technologies: Principles and Applications.Cold Spring Harbor perspectives in biology · 2016Review
- Systematic comparison of CRISPR/Cas9 and RNAi screens for essential genes.Nature biotechnology · 2016Article
- In vivo blunt-end cloning through CRISPR/Cas9-facilitated non-homologous end-joining.Nucleic acids research · 2016Article
19 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
4 authors at 1 institution in 1 country.
Funding
Abstract
Zinc finger nucleases (ZFNs) have been used successfully to create genome-specific double-strand breaks and thereby stimulate gene targeting by several thousand fold. ZFNs are chimeric proteins composed of a specific DNA-binding domain linked to a non-specific DNA-cleavage domain. By changing key residues in the recognition helix of the specific DNA-binding domain, one can alter the ZFN binding specificity and thereby change the sequence to which a ZFN pair is being targeted. For these and other reasons, ZFNs are being pursued as reagents for genome modification, including use in gene therapy. In order for ZFNs to reach their full potential, it is important to attenuate the cytotoxic effects currently associated with many ZFNs. Here, we evaluate two potential strategies for reducing toxicity by regulating protein levels. Both strategies involve creating ZFNs with shortened half-lives and then regulating protein level with small molecules. First, we destabilize ZFNs by linking a ubiquitin moiety to the N-terminus and regulate ZFN levels using a proteasome inhibitor. Second, we destabilize ZFNs by linking a modified destabilizing FKBP12 domain to the N-terminus and regulate ZFN levels by using a small molecule that blocks the destabilization effect of the N-terminal domain. We show that by regulating protein levels, we can maintain high rates of ZFN-mediated gene targeting while reducing ZFN toxicity.
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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.