High efficiency gene correction in hematopoietic cells by donor-template-free CRISPR/Cas9 genome editing

  • 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.
Author:Duran Sürün, Joachim SchwäbleGND, Ana Tomasovic, Roy Ehling, Stefan Stein, Nina Susanne KurrleORCiDGND, Harald von Melchner, Frank SchnütgenORCiDGND
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29499925
Parent Title (English):Molecular therapy. Nucleic Acids
Publisher:Nature Publ. Group
Place of publication:New York, NY
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/11/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/03/08
Tag:CGD; CRISPR/Cas9; NHEJ; chronic granulomatous disease; hematopoietic cells; in situ gene correction; non-homologous end joining
Page Number:8
First Page:1
Last Page:8
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Zum Teil auch Dissertation, Darmstadt, Technische Universität Darmstadt, 2018
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0