Scientists have found they can use a genome-editing technique to increase hemoglobin production, and they described this method in Nature Communications.
The team used transcription activator-like effector nucleases (TALENs) to introduce the hereditary persistence of fetal hemoglobin (HPFH)-175T4C point mutation into erythroid cell lines.
This served to switch on the fetal hemoglobin gene and increase hemoglobin production.
“Our laboratory study provides a proof of concept that changing just one letter of DNA in a gene could alleviate the symptoms of sickle cell anemia and thalassemia—inherited diseases in which people have damaged hemoglobin,” said Merlin Crossley, PhD, of the University of New South Wales in Sydney, Australia.
“Because the good genetic variation we introduced already exists in nature, this approach should be effective and safe. However, more research is needed before it can be tested in people as a possible cure for serious blood diseases.”
Dr Crossley and his colleagues introduced the HPFH-175T4C point mutation into erythroid cell lines using TALENs, which can be designed to cut a gene at a specific point, as well as provide the desired piece of donor DNA for insertion.
“Breaks in DNA can be lethal to cells, so they have in-built machinery to repair any nicks as soon as possible, by grabbing any spare DNA that seems to match . . . ,” Dr Crossley explained.
“We exploited this effect. When our genome-editing protein cuts the DNA, the cell quickly replaces it with the donor DNA that we have also provided.”
The researchers pointed out that the HPFH-175T4C point mutation increased fetal globin expression via de novo recruitment of the activator TAL1, which promoted chromatin looping of distal enhancers to the modified γ-globin promoter.
The team also said that, if their editing technique proves safe and effective in hematopoietic stem cells, it could offer significant advantages over other approaches used to treat hemoglobin disorders, such as conventional gene therapy.
