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Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and mammalian cells

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Durai, S.·2005·Nucleic Acids Research
DOI 10.1093/nar/gki912PMC PMC1270952
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Abstract

Custom-designed zinc finger nucleases (ZFNs), proteins designed to cut at specific DNA sequences, are becoming powerful tools in gene targeting--the process of replacing a gene within a genome by homologous recombination (HR). ZFNs that combine the non-specific cleavage domain (N) of FokI endonuclease with zinc finger proteins (ZFPs) offer a general way to deliver a site-specific double-strand break (DSB) to the genome. The development of ZFN-mediated gene targeting provides molecular biologists with the ability to site-specifically and permanently modify plant and mammalian genomes including the human genome via homology-directed repair of a targeted genomic DSB. The creation of designer ZFNs that cleave DNA at a pre-determined site depends on the reliable creation of ZFPs that can specifically recognize the chosen target site within a genome. The (Cys2His2) ZFPs offer the best framework for developing custom ZFN molecules with new sequence-specificities. Here, we explore the different approaches for generating the desired custom ZFNs with high sequence-specificity and affinity. We also discuss the potential of ZFN-mediated gene targeting for 'directed mutagenesis' and targeted 'gene editing' of the plant and mammalian genome as well as the potential of ZFN-based strategies as a form of gene therapy for human therapeutics in the future.

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  • Different endonucleases employed as second generation tools include zinc finger nucleases (ZFN), meganucleases, TALEN, and CRISPR/Cas9.

    “As second generation tools, different endonucleases have been employed.This category includes zinc finger nucleases (ZFN), meganucleases, transcription activators like effectors nucleases (TALEN) and CRISPR/Cas9 (Durai et al., 2005;Porteus and Carroll 2005;Cabaniols et al., 2010;Silva et al., 2011;Kim et al., 2012;Sanjana et al., 2012;Cho et al., 2013;Sun and Zhao, 2013).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Durai et al., 2005

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Authors
Durai, S.
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2005-10-12
Volume
33
Issue
18
Pages
5978-5990
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gki912
PMC
PMC1270952
OpenAlex
W2123502778
Cited by
522
References
5
Citations by year
2026: 8 · 2025: 24 · 2024: 27 · 2023: 26 · 2022: 29 · 2021: 23 · 2020: 22 · 2019: 13 · 2018: 29 · 2017: 25 · 2016: 30 · 2015: 25 · 2014: 27 · 2013: 33 · 2012: 28
FWCI
1.51
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Nucleic Acids Research (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Johns Hopkins University
  • National Institutes of Health
  • Center for AIDS Research, University of Washington
  • National Institute of General Medical Sciences (R01GM053923, GM 53923)
  • National Institute of Allergy and Infectious Diseases (P30AI42855, P30AI042855)
  • National Institute of Environmental Health Sciences (ES03819, P30ES003819)
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 › RNA regulation and disease
Keywords
zinc finger nucleases, gene targeting, homologous recombination, homology-directed repair, zinc finger proteins, C2H2 zinc finger, site-specific DNA cleavage, DNA double-strand breaks, genome editing, directed mutagenesis, gene therapy, plant genome engineering, human genome modification
MeSH terms
Animals, DNA Repair, DNA-Binding Proteins, Genetic Engineering, Humans, Deoxyribonucleases, Type II Site-Specific, Genome, Human, Zinc Fingers, Gene Targeting, Genome, Plant, Catalytic Domain, Genomics

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