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

Beeke Wienert, Alister P. W. Funnell, Laura J. Norton, Richard C. M. Pearson, Lorna E. Wilkinson-White, Krystal Lester, Jim Vadolas, Matthew H. Porteus, Jacqueline M. Matthews, Kate G. R. Quinlan and Merlin Crossley ()
Additional contact information
Beeke Wienert: School of Biotechnology and Biomolecular Sciences, University of New South Wales
Alister P. W. Funnell: School of Biotechnology and Biomolecular Sciences, University of New South Wales
Laura J. Norton: School of Biotechnology and Biomolecular Sciences, University of New South Wales
Richard C. M. Pearson: School of Biotechnology and Biomolecular Sciences, University of New South Wales
Lorna E. Wilkinson-White: School of Molecular Bioscience, The University of Sydney
Krystal Lester: School of Molecular Bioscience, The University of Sydney
Jim Vadolas: Cell and Gene Therapy Research Group, Murdoch Childrens Research Institute, Royal Children’s Hospital
Matthew H. Porteus: Stanford University
Jacqueline M. Matthews: School of Molecular Bioscience, The University of Sydney
Kate G. R. Quinlan: School of Biotechnology and Biomolecular Sciences, University of New South Wales
Merlin Crossley: School of Biotechnology and Biomolecular Sciences, University of New South Wales

Nature Communications, 2015, vol. 6, issue 1, 1-8

Abstract: Abstract 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms8085 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8085

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8085

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().