TY  - JOUR
A1  - Sürün, Duran
A1  - Schwäble, Joachim
A1  - Tomasovic, Ana
A1  - Ehling, Roy
A1  - Stein, Stefan
A1  - Kurrle, Nina Susanne
A1  - Melchner, Harald von
A1  - Schnütgen, Frank
T1  - High efficiency gene correction in hematopoietic cells by donor-template-free CRISPR/Cas9 genome editing
T2  - Molecular therapy. Nucleic Acids
N2  - 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.
KW  - CRISPR/Cas9
KW  - non-homologous end joining
KW  - NHEJ
KW  - in situ gene correction
KW  - hematopoietic cells
KW  - chronic granulomatous disease
KW  - CGD
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45826
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-458262
SN  - 2162-2531
N1  - This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
N1  - Zum Teil auch Dissertation, Darmstadt, Technische Universität Darmstadt, 2018
VL  - 10
SP  - 1
EP  - 8
PB  - Nature Publ. Group
CY  - New York, NY
ER  -