Cited by 1,076CRISPR and Genetic EngineeringRNA regulation and diseaseRNA Interference and Gene Delivery

Genome Engineering With Zinc-Finger Nucleases

Open access
Carroll, Dana·2011·Genetics

Abstract

Zinc-finger nucleases (ZFNs) are targetable DNA cleavage reagents that have been adopted as gene-targeting tools. ZFN-induced double-strand breaks are subject to cellular DNA repair processes that lead to both targeted mutagenesis and targeted gene replacement at remarkably high frequencies. This article briefly reviews the history of ZFN development and summarizes applications that have been made to genome editing in many different organisms and situations. Considerable progress has been made in methods for deriving zinc-finger sets for new genomic targets, but approaches to design and selection are still being perfected. An issue that needs more attention is the extent to which available mechanisms of double-strand break repair limit the scope and utility of ZFN-initiated events. The bright prospects for future applications of ZFNs, including human gene therapy, are discussed.

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Crossref · 10.1534/genetics.111.131433

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  • ZNF creates targeted double-strand breaks, commonly producing frameshift or nonsense mutations that create null alleles.

    “The ZNF techniques preceded CRSISPR but work similarly in that the ZNF creates targeted double stranded breaks in the sequence of interest with a common outcome being the generation of a frameshift or nonsense mutation creating a null allele (Carroll, 2011).”

    From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Carroll, 2011

    The Abstract and “Stimulating Gene Targeting With Double-Strand Breaks” describe targeted ZFN-induced breaks and mutations produced when those breaks are repaired. The latter section identifies deletions, insertions, and substitutions, but does not say that frameshift or nonsense mutations commonly result or that they create null alleles. No page numbers were available in our copy. (LLM, conf=0.84)

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Cites

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Research works printed but not linked: 15

  1. Beumer, K. J., J. K. Trautman, A. Bozas, J.-L. Liu, J. Rutter, et al., 2008 Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases. Proc. Natl. Acad. Sci. USA 105: 19821-19826.
  2. Bitinaite, J., D. A. Wah, A. K. Aggarwal, and I. Schildkraut, 1998 FokI dimerization is required for DNA cleavage. Proc. Natl. Acad. Sci. USA 95: 10570-10575.
  3. Kim, Y.-G., and S. Chandrasegaran, 1994 Chimeric restriction en- donuclease. Proc. Natl. Acad. Sci. USA 91: 883-887.
  4. Kim, Y.-G., J. Cha, and S. Chandrasegaran, 1996 Hybrid restric- tion enzymes: zinc finger fusions to FokI cleavage domain. Proc. Natl. Acad. Sci. USA 93: 1156-1160.
  5. Li, L., L. P. Wu, and S. Chandrasegaran, 1992 Functional domains in FokI restriction endonuclease. Proc. Natl. Acad. Sci. USA 89: 4275-4279.
  6. Lloyd, A., C. L. Plaisier, D. Carroll, and G. N. Drews, 2005 Tar- geted mutagenesis using zinc-finger nucleases in Arabidopsis. Proc. Natl. Acad. Sci. USA 102: 2232-2237.
  7. Meyer, M., M. Hrabé de Angelis, W. Wurst, and R. Kühn, 2010 Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases. Proc. Natl. Acad. Sci. USA 107: 15022-15026.
  8. Moore, M., A. Klug, and Y. Choo, 2001 Improved DNA binding specificity from polyzinc finger peptides by using strings of two- finger units. Proc. Natl. Acad. Sci. USA 98: 1437-1441.
  9. Morton, J., M. W. Davis, E. M. Jorgensen, and D. Carroll, 2006 Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Proc. Natl. Acad. Sci. USA 103: 16370-16375.
  10. Osakabe, K., Y. Osakabe, and S. Toki, 2010 Site-directed muta- genesis in Arabidopsis using custom-designed zinc finger nu- cleases. Proc. Natl. Acad. Sci. USA 107: 12034-12039.
  11. Santiago, Y., E. Chan, P.-Q. Liu, S. Orlando, L. Zhang, et al., 2008 Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases. Proc. Natl. Acad. Sci. USA 105: 5809-5814.
  12. Scherer, S., and R. W. Davis, 1979 Replacement of chromosome segments with altered DNA sequences constructed in vitro. Proc. Natl. Acad. Sci. USA 76: 4951-4955.
  13. Vasquez, K. M., K. Marburger, Z. Intody, and J. H. Wilson, 2001 Manipulating the mammalian genome by homologous recombination. Proc. Natl. Acad. Sci. USA 98: 8403-8410.
  14. Young, J. J., J. M. Cherone, Y. Doyon, I. Ankoudinova, F. M. Faraji et al., 2011 Efficient targeted gene disruption in the soma and germ line of the frog Xenopus tropicalis using engineered zinc- finger nucleases. Proc. Natl. Acad. Sci. USA 108: 7052-7057.
  15. Zhang, F., M. L. Maeder, E. Unger-Wallace, J. P. Hoshaw, D. Reyon, et al., 2010 High frequency targeted mutagenesis in Arabidop- sis thaliana using zinc finger nucleases. Proc. Natl. Acad. Sci. USA 107: 12028-12033.

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Authors
Carroll, D.
Affiliations
University of Utah (US)
Corresponding author
Carroll, Dana
Venue
Genetics
Published
2011-08-01
Volume
188
Issue
4
Pages
773-782
ISSN
  • 0016-6731 (ISSN-L)
  • 1943-2631
OpenAlex
W2123196886
Cited by
1,076
References
5
Citations by year
2026: 41 · 2025: 86 · 2024: 95 · 2023: 89 · 2022: 74 · 2021: 79 · 2020: 83 · 2019: 59 · 2018: 60 · 2017: 67 · 2016: 60 · 2015: 68 · 2014: 73 · 2013: 84 · 2012: 51
FWCI
6.21
Type
journal article
Language
en
Open access
Locations
  • Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM58504, GM078571, R01GM078571, R01GM058504)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
zinc finger nucleases, genome editing, targeted mutagenesis, targeted gene replacement, DNA double-strand break repair, human gene therapy, gene targeting
MeSH terms
Animals, Endonucleases, Genetic Engineering, Humans, Substrate Specificity, Zinc Fingers, Genome, Gene Targeting, DNA Breaks, Double-Stranded

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