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Cited by 39CRISPR and Genetic EngineeringVirus-based gene therapy researchCAR-T cell therapy research

High Efficiency Gene Correction in Hematopoietic Cells by Donor-Template-Free CRISPR/Cas9 Genome Editing

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Sürün, Duran, Schwäble, Joachim, Tomasovic, Ana, Ehling, Roy, Stein, Stefan, Kurrle, Nina, von Melchner, Harald, Schnütgen, Frank·2018·Molecular Therapy Nucleic Acids
DOI 10.1016/j.omtn.2017.11.001PMC PMC5723376
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Abstract

The CRISPR/Cas9 prokaryotic adaptive immune system and its swift repurposing for genome editing enables modification of any prespecified genomic sequence with unprecedented accuracy and efficiency, including targeted gene repair. We used the CRISPR/Cas9 system for targeted repair of patient-specific point mutations in the Cytochrome b-245 heavy chain gene (CYBB), whose inactivation causes chronic granulomatous disease (XCGD)-a life-threatening immunodeficiency disorder characterized by the inability of neutrophils and macrophages to produce microbicidal reactive oxygen species (ROS). We show that frameshift mutations can be effectively repaired in hematopoietic cells by non-integrating lentiviral vectors carrying RNA-guided Cas9 endonucleases (RGNs). Because about 25% of most inherited blood disorders are caused by frameshift mutations, our results suggest that up to a quarter of all patients suffering from monogenic blood disorders could benefit from gene therapy employing personalized, donor template-free RGNs.

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Cited by

Sorted by citations

Authors
Sürün, D., Schwäble, J., Tomasovic, A., Ehling, R., Stein, S., Kurrle, N., von Melchner, H., & Schnütgen, F.
Affiliations
  • Goethe University Frankfurt (DE)
  • Georg Speyer Haus (DE)
Corresponding author
Sürün, Duran
ORCID
Venue
Molecular Therapy Nucleic Acids
Publisher
Elsevier BV
Published
2018-03
Volume
10
Pages
1-8
ISSN
2162-2531 (ISSN-L)
DOI
10.1016/j.omtn.2017.11.001
PMC
PMC5723376
OpenAlex
W2770597766
Cited by
39
References
4
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 10 · 2019: 10 · 2018: 5
FWCI
2.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy — Nucleic Acids (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
Funders
  • Bundesministerium für Bildung und Forschung (NGFNplus-DiGtoPconsortium / 01GS0858)
  • Deutsche Forschungsgemeinschaft (ME 820/6- 1, SCHN1166/4-1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
Keywords
CRISPR/Cas9 genome editing, CYBB, chronic granulomatous disease, hematopoietic cells, gene therapy, point mutations

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