ArticleGenome research2012
Targeted gene addition to a predetermined site in the human genome using a ZFN-based nicking enzyme.
Article in Genome research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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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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Who cites it
76 citing papers in PubMed, 134 citations in OpenAlex.
- Advances in Double-Stranded DNA Targeting Technologies.Exploration (Beijing, China) · 2026Review
- Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells.Nature communications · 2024Article
- Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.Nature communications · 2023Article
- HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022Review
- The State-of-the-Art of Gene Editing and its Application to Viral Infections and Diseases Including COVID-19.Frontiers in cellular and infection microbiology · 2022Review
- STAT5 as a Key Protein of Erythropoietin Signalization.International journal of molecular sciences · 2021Review
- Rational Selection of CRISPR-Cas9 Guide RNAs for Homology-Directed Genome Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Expanding the editable genome and CRISPR-Cas9 versatility using DNA cutting-free gene targeting based on in trans paired nicking.Nucleic acids research · 2020Article
- Adenovirus vectors in hematopoietic stem cell genome editing.FEBS letters · 2019Review
- CRISPR-Cas9 genome editing induces megabase-scale chromosomal truncations.Nature communications · 2019Article
- Review
- Initiation of homologous recombination at DNA nicks.Nucleic acids research · 2018Review
- HDAd5/35Molecular therapy. Methods & clinical development · 2018Article
- Engineering altered protein-DNA recognition specificity.Nucleic acids research · 2018Review
- Inhibition of 53BP1 favors homology-dependent DNA repair and increases CRISPR-Cas9 genome-editing efficiency.Nature biotechnology · 2018Article
- Genome Editing Redefines Precision Medicine in the Cardiovascular Field.Stem cells international · 2018Review
- Assaying Repair at DNA Nicks.Methods in enzymology · 2018Article
- Optimized guide RNA structure for genome editing via Cas9.Oncotarget · 2017Article
- In trans paired nicking triggers seamless genome editing without double-stranded DNA cutting.Nature communications · 2017Article
- Control of gene editing by manipulation of DNA repair mechanisms.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zinc-finger nucleases (ZFNs) drive highly efficient genome editing by generating a site-specific DNA double-strand break (DSB) at a predetermined site in the genome. Subsequent repair of this break via the nonhomologous end-joining (NHEJ) or homology-directed repair (HDR) pathways results in targeted gene disruption or gene addition, respectively. Here, we report that ZFNs can be engineered to induce a site-specific DNA single-strand break (SSB) or nick. Using the CCR5-specific ZFNs as a model system, we show that introduction of a nick at this target site stimulates gene addition using a homologous donor template but fails to induce significant levels of the small insertions and deletions (indels) characteristic of repair via NHEJ. Gene addition by these CCR5-targeted zinc finger nickases (ZFNickases) occurs in both transformed and primary human cells at efficiencies of up to ∼1%-8%. Interestingly, ZFNickases targeting the AAVS1 "safe harbor" locus revealed similar in vitro nicking activity, a marked reduction of indels characteristic of NHEJ, but stimulated far lower levels of gene addition-suggesting that other, yet to be identified mediators of nick-induced gene targeting exist. Introduction of site-specific nicks at distinct endogenous loci provide an important tool for the study of DNA repair. Moreover, the potential for a SSB to direct repair pathway choice (i.e., HDR but not NHEJ) may prove advantageous for certain therapeutic applications such as the targeted correction of human disease-causing mutations.
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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.