The DOI matches its Crossref record; 36 of the 37 references it cites were found in a registry or an index.
Custom Zinc-Finger Nucleases for Use in Human Cells
Open accessAbstract
Genome engineering through homologous recombination (HR) is a powerful instrument for studying biological pathways or creating treatment options for genetic disorders. In mammalian cells HR is rare but the creation of targeted DNA double-strand breaks stimulates HR significantly. Here, we present a method to generate, evaluate, and optimize rationally designed endonucleases that promote HR. The DNA-binding domains were synthesized by assembling predefined zinc-finger modules selected by phage display. Attachment of a transcriptional activation domain allowed assessment of DNA binding in reporter assays, while fusion with an endonuclease domain created custom nucleases that were tested for their ability to stimulate HR in episomal and chromosomal gene repair assays. We demonstrate that specificity, expression kinetics, and protein design are crucial parameters for efficient gene repair and that our two-step assay allows one to go quickly from design to testing to successful employment of the custom nucleases in human cells.
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In the citing paper
“For example, if the nuclease action mutates unintended targets that are important for cellular physiology, the treated cells may become dysfunctional or even die [61,62,63].”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [63]
In the citing paper
“The fundamental safety concern for using ZFN mediated gene disruption for human therapy is the specificity of gene targeting.”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [63]
Citations
Cites
Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain.
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A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency
Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M., Le Deist, F., Wulffraat, N., McIntyre, E., Radford, I., Villeval, J.-L., Fraser, C. C., Cavazzana-Calvo, M., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejm200301163480314 · Cited by 1,867 · cited 1×
“Moreover, random integration can have genotoxic side effects by disrupting cellular genes or by misregulating expression of nearby genes, as recently shown in a gene therapy trial involving randomly integrating retroviral vectors [1–4].”
BackgroundHighly efficient endogenous human gene correction using designed zinc-finger nucleases
Urnov, F. D., Miller, J. C., Lee, Y.-L., Beausejour, C. M., Rock, J. M., Augustus, S., Jamieson, A. C., Porteus, M. H., Gregory, P. D., & Holmes, M. C. (2005) · Nature · doi:10.1038/nature03556 · Cited by 1,642
Sustained Correction of X-Linked Severe Combined Immunodeficiency by ex Vivo Gene Therapy
Hacein‐Bey‐Abina, S., Deist, F. L., Carlier, F., Bouneaud, C., Hue, C., de Villartay, J., Thrasher, A. J., Wulffraat, N. M., Sorensen, R., Dupuis‐Girod, S., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012616 · Cited by 1,098
Enhancing Gene Targeting with Designed Zinc Finger Nucleases
Bibikova, M. V., Beumer, K. J., Trautman, J. K., & Carroll, D. (2003) · Science · doi:10.1126/science.1079512 · Cited by 824
Chimeric nucleases stimulate gene targeting in human cells
Porteus, M. H., & Baltimore, D. (2003) · Science · doi:10.1126/science.1078395 · Cited by 741
Rouet, P., Smih, F., & Jasin, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8096 · Cited by 739
Stimulation of Homologous Recombination through Targeted Cleavage by Chimeric Nucleases
Bibikova, M. V., Carroll, D., Segal, D. J., Trautman, J. K., Smith, J., Kim, Y., & Chandrasegaran, S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.1.289-297.2001 · Cited by 614
Beerli, R. R., Segal, D. J., Dreier, B., & Barbas, C. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14628 · Cited by 539
Genetic Steps of Mammalian Homologous Repair with Distinct Mutagenic Consequences
Stark, J. M., Pierce, A. J., Oh, J., Pastink, A., & Jasin, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.21.9305-9316.2004 · Cited by 501
Cited by
Sorted by citations
Genome Engineering With Zinc-Finger Nucleases
Carroll, D. (2011) · Genetics · doi:10.1534/genetics.111.131433 · Cited by 1,076
Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases
Meng, X., Noyes, M. B., Zhu, L. J., Lawson, N. D., & Wolfe, S. A. (2008) · Nature Biotechnology · doi:10.1038/nbt1398 · Cited by 741
A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity
Mussolino, C., Morbitzer, R., Lütge, F., Dannemann, N., Lahaye, T., & Cathomen, T. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr597 · Cited by 714
Maeder, M. L., Thibodeau-Beganny, S., Osiak, A., Wright, D. A., Anthony, R. M., Eichtinger, M., Jiang, T., Foley, J. E., Winfrey, R. J., Townsend, J. A., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.06.016 · Cited by 727
Durai, S. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki912 · Cited by 522
Metadata
- Authors
- Alwin, S., Gere, M. B., Guhl, E., Effertz, K., Barbas, C. F., Segal, D. J., Weitzman, M. D., & Cathomen, T.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Scripps Research Institute (US)
- University of Arizona (US)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Cathomen, Toni
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 12
- Issue
- 4
- Pages
- 610-617
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W1999295945
- Cited by
- 165
- References
- 37
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 19
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Funders
- National Cancer Institute (R21CA103651)
- National Institute of General Medical Sciences (R01GM065059)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- zinc finger nucleases, homologous recombination, genome editing, DNA double-strand breaks, phage display, transactivation domain, gene repair, human cells, nuclease specificity, expression kinetics
- MeSH terms
- Base Sequence, Binding Sites, DNA, DNA Nucleotidyltransferases, DNA Repair, DNA-Binding Proteins, Endonucleases, Humans, Molecular Sequence Data, Promoter Regions, Genetic, Recombination, Genetic, Zinc Fingers, Gene Targeting
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