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

Sürün D, Schwäble J, Tomasovic A, Ehling R, Stein S, Kurrle N, von Melchner H, Schnütgen F
Molecular therapy. Nucleic acids 2018; 102018Mar02: 1-8


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.

Zugehörigkeit: Department of Molecular Hematology, Goethe University Medical School, 60590 Frankfurt am Main, Germany; LOEWE Center for Cell and Gene Therapy, Goethe University Medical School, 60590 Frankfurt am Main, Germany. Electronic address: d.sueruen@med.uni-frankfurt.de.

Aritkel auf PubMed

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