Editing the genome to introduce a beneficial naturally occurring mutation associated with increased fetal globin.

Autor:	Wienert B; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia., Funnell AP; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia., Norton LJ; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia., Pearson RC; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia., Wilkinson-White LE; School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia., Lester K; School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia., Vadolas J; 1] Cell and Gene Therapy Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia [2] Department of Paediatrics, University of Melbourne, Parkville, Victoria 3052, Australia., Porteus MH; Department of Pediatrics, Stanford University, Stanford, California 94304, USA., Matthews JM; School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia., Quinlan KG; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia., Crossley M; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2015 May 14; Vol. 6, pp. 7085. Date of Electronic Publication: 2015 May 14.
DOI:	10.1038/ncomms8085
Abstrakt:	Genetic disorders resulting from defects in the adult globin genes are among the most common inherited diseases. Symptoms worsen from birth as fetal γ-globin expression is silenced. Genome editing could permit the introduction of beneficial single-nucleotide variants to ameliorate symptoms. Here, as proof of concept, we introduce the naturally occurring Hereditary Persistance of Fetal Haemoglobin (HPFH) -175T>C point mutation associated with elevated fetal γ-globin into erythroid cell lines. We show that this mutation increases fetal globin expression through de novo recruitment of the activator TAL1 to promote chromatin looping of distal enhancers to the modified γ-globin promoter.
Databáze:	MEDLINE
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