Nicosia, Cyprus. Researchers at the Cyprus Institute of Neurology and Genetics (CING) presented a gene-editing strategy aimed at improving treatment options for beta-thalassaemia. The work was published in the international journal Genome Biology.
Study and research leadership
CING researchers on Friday unveiled a novel gene-editing strategy that could transform care for patients with beta-thalassaemia, a common inherited blood disorder in Cyprus, according to a study led by researcher Nicoletta Papaioannou, formerly of the Department of Genetic Haematological Diseases and Thalassaemia at CING.
Duplex base editing and haemoglobin effects
The study demonstrates that duplex base editing, a dual base-editing technique, can induce a therapeutic increase in foetal haemoglobin (HbF) while preserving high levels of genomic integrity.
Background on beta-thalassaemia
Beta-thalassaemia, also known as Mediterranean anaemia, results from mutations in the HBB gene, which is responsible for producing beta-globin. Dysfunction of this gene leads to lifelong anaemia and necessitates regular blood transfusions.
Therapeutic focus and haemoglobin switching
The therapy focuses on raising gamma-globin, a key component of HbF, which naturally decreases after birth through haemoglobin switching. Targeting the genes that regulate this process offers a promising therapeutic pathway.
Collaboration and methodology
In the study titled Functional correction and genome integrity with duplex base editing of beta-thalassaemic hematopoietic stem cells, CING researchers, in collaboration with thalassaemia clinics in Nicosia and Larnaca and the University Medical Centre Freiburg in Germany, applied the base-editing technology to patient-derived haematopoietic stem cells.
2×BE approach and comparison therapies
The team developed a 2×BE approach, simultaneously targeting the erythroid enhancer of BCL11A and the promoter of the HBG gene. This method was compared with single-gene targeting and the approved CASGEVY™ therapy, based on CRISPR/Cas9 technology.
Results and HbF expression levels
Results showed HbF expression reaching 56.68 per cent, a 6.4-fold increase over unedited cells, surpassing the therapeutic threshold of 30 per cent.
Safety assessments and genome integrity
Genome-wide safety assessments indicated that, unlike double-strand break technologies, duplex base editing presents a significantly reduced risk of chromosomal rearrangements, with no observed gene misplacements between BCL11A and HBG.
Potential applications
The study positions duplex base editing as an effective and safe therapeutic strategy for beta-thalassaemia, with potential applications in other genetic disorders.
What do you think this research could mean for future gene-editing treatments in Cyprus?