Program in Molecular Medicine
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetics and Genomics | Hemic and Lymphatic Diseases | Nanomedicine
The blood disorder, beta-thalassaemia, is considered an attractive target for gene correction. Site-specific triplex formation has been shown to induce DNA repair and thereby catalyse genome editing. Here we report that triplex-forming peptide nucleic acids (PNAs) substituted at the gamma position plus stimulation of the stem cell factor (SCF)/c-Kit pathway yielded high levels of gene editing in haematopoietic stem cells (HSCs) in a mouse model of human beta-thalassaemia. Injection of thalassemic mice with SCF plus nanoparticles containing gammaPNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood haemoglobin levels into the normal range, reduced reticulocytosis, reversal of splenomegaly and up to 7% beta-globin gene correction in HSCs, with extremely low off-target effects. The combination of nanoparticle delivery, next generation gammaPNAs and SCF treatment may offer a minimally invasive treatment for genetic disorders of the blood that can be achieved safely and simply by intravenous administration.
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DOI of Published Version
Nat Commun. 2016 Oct 26;7:13304. doi: 10.1038/ncomms13304. Link to article on publisher's site
Bahal, Raman; Greiner, Dale L.; Brehm, Michael A.; and Glazer, Peter M., "In vivo correction of anaemia in beta-thalassemic mice by gammaPNA-mediated gene editing with nanoparticle delivery" (2016). Open Access Articles. 2968.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.