Cited by 292CRISPR and Genetic EngineeringRNA Interference and Gene DeliveryDNA and Nucleic Acid Chemistry

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In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence

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Choo, Yen, Sánchez-García, Isidro, Klug, Aaron·1994·Nature

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Abstract

A DNA-binding peptide comprising three zinc-fingers has been engineered to bind specifically to a unique nine-base-pair region of a BCR-ABL fusion oncogene in preference to the parent genomic sequences. Binding to the target oncogene in chromosomal DNA is possible in transformed cells in culture, and results in blockage of transcription. Consequently, murine cells rendered independent of growth factors by the action of the oncogene revert to factor dependence upon transient transfection with a vector expressing the peptide.

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Regulation of gene expression: probing DNA–protein interactionsin vivoandin vitro
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Recognition of DNA by single-chain derivatives of the phage 434 repressor: high affinity binding depends on both the contacted and non- contacted base pairs
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Repression of the human immunodeficiency virus type 1 promoter by the human KRAB domain results in inhibition of virus production
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Philadelphia-Positive B-Cell Acute Lymphoblastic Leukemia Is Initiated in an Uncommitted Progenitor Cell
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Self-citation
Binding Properties of the Artificial Zinc Fingers Coding Gene Sint1
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Neutralizing the function of a β-globin–associated cis -regulatory DNA element using an artificial zinc finger DNA-binding domain
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“Klug and colleagues first described the use of a synthetic 3-ZF protein that blocked the activating sequence that arose from a chromosomal translocation (10).”
Background
Finding the Missing Code of RNA Recognition by PUF Proteins
Chen, Y., & Varani, G. (2011) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.07.001 · Cited by 14
“About 20 years ago, Yen Choo and Aaron Klug reported the application of engineered zing finger proteins to bind to a desired DNA sequence and alter gene transcription (Choo et al., 1994).”
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Les domaines à doigts de zinc
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“Ainsi l’ARN polymérase (Figure 3A-I) a été bloquée lors de l’utilisation d’une ZFP de trois motifs ZF bloquant l’expression de la protéine oncogène p190BCR-ABL [20].”
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Background
Diversification of the CRISPR Toolbox: Applications of CRISPR-Cas Systems Beyond Genome Editing
Balderston, S., Clouse, G., Ripoll, J. J., Pratt, G. K., Gasiūnas, G., Bock, J.-O., Bennett, E., & Aran, K. (2021) · The CRISPR Journal · doi:10.1089/crispr.2020.0137 · Cited by 14
Dissecting the function of the adult β-globin downstream promoter region using an artificial zinc finger DNA-binding domain
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“Artificial DNA-binding proteins comprising zinc finger domains can surmount this challenge (35,36).”
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Genetic variants in the ZNF208 gene are associated with esophageal cancer in a Chinese Han population
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“ZNF208 is a member of the Zinc finger family of proteins, which bind to DNA through a series of zinc finger motifs and regulate gene transcription [11, 12].”
Background
Binding of Organometallic Ruthenium Anticancer Complexes to DNA: Thermodynamic Base and Sequence Selectivity
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“Preclinical studies have demonstrated successful control using ZFP for such a repertoire [113].”
Background

Authors: Choo, Y., Sánchez-García, I., & Klug, A.
Affiliations: MRC Laboratory of Molecular Biology (GB)
ORCID: Choo, Yen
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1994-12
Volume: 372
Issue: 6507
Pages: 642-645
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/372642a0
OpenAlex: W2019616754
Cited by: 292
References: 36
Citations by year: 2026: 1 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 9 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 11 · 2013: 1 · 2012: 6
FWCI: 7.35
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords: zinc finger DNA-binding protein, transcriptional repression, site-specific DNA binding, growth factor independence, transformed cells, transcriptional block
MeSH terms: Amino Acid Sequence, Animals, Cell Line, DNA, DNA-Binding Proteins, Feasibility Studies, Gene Expression Regulation, Humans, Molecular Sequence Data, Protein Binding, Recombinant Fusion Proteins, Transcription, Genetic, Transfection, Fusion Proteins, bcr-abl, Zinc Fingers, Mice

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In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence

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