Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding
- Journal:
- Nature Genetics
- Published:
- DOI:
- 10.1038/s41588-018-0085-0
- Affiliations:
- 3
- Authors:
- 12
Research Highlight
A ‘natural’ gene therapy for blood disorders
© Narupon Promvichai/EyeEm/Getty
By reproducing naturally occurring mutations that elevate the production of foetal haemoglobin, a new CRISPR-based gene therapy could help treat inherited blood disorders such as sickle cell disease and β-thalassemia.
The mutations are found in patients with a benign condition called ‘hereditary persistence of foetal haemoglobin’, or HPFH, in which the γ-globin that is normally switched off after birth remains active.
A team led by scientists at the University of New South Wales identified two repressor proteins that normally bind part of the γ-globin gene at specific sites where mutations responsible for HPFH occur.
Using CRISPR gene-editing technology, they introduced HPFH-associated mutations into blood-forming cells and saw elevated expression of the γ-globin gene.
This finding helps clarify how these mutations prevent gene silencing, and it highlights a potential way to reactivate foetal haemoglobin production using genetic changes known to be safe in people.
References
- Nature Genetics 50, 498–503 (2018). doi: 10.1038/s41588-018-0085-0
Institutions | Authors | Share |
---|---|---|
University of New South Wales (UNSW Sydney), Australia | 0.83 | |
Japanese Red Cross Society, Japan | 0.08 | |
RIKEN BioResource Research Center (BRC), Japan | 0.08 |