{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:00:02Z","timestamp":1790460002182,"version":"4.1.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genome Ed."],"abstract":"<jats:p>\u03b2-Thalassaemia is caused by over 300 mutations in and around the \u03b2-globin gene that lead to impaired synthesis of \u03b2-globin. The expression of \u03b1-globin continues normally, resulting in an excess of \u03b1-globin chains within red blood cells and their precursors. These unpaired \u03b1-globin chains form unstable \u03b1-hemichromes that trigger cascades of events to generate reactive oxygen species, leading to ineffective erythropoiesis and haemolysis in patients with \u03b2-thalassaemia. The clinical genetic data reported over several decades have demonstrated how the coinheritance of \u03b1-thalassaemia ameliorates the disease phenotype of \u03b2-thalassaemia. Thus, it is evident that down-regulation of the \u03b1-globin gene expression in patients with \u03b2-thalassaemia could ameliorate or even cure \u03b2-thalassaemia. Over the last few years, significant progress has been made in utilising this pathway to devise a cure for \u03b2-thalassaemia. Most research has been done to alter the epigenetic landscape of the \u03b1-globin locus or the well-characterised distant enhancers of \u03b1-globin. In vitro, pre-clinical studies on primary human erythroid cells have unveiled inhibition of histone lysine demethylation and histone deacetylation as potential targets to achieve selective downregulation of \u03b1-globin through epigenetic drug targeting. CRISPR based genome editing has been successfully used in vitro to mutate \u03b1-globin genes or enhancers of \u03b1-goblin to achieve clinically significant knockdowns of \u03b1-globin to the levels beneficial for patients with \u03b2-thalassaemia. This review summarises the current knowledge on the regulation of human \u03b1-globin genes and the clinical genetic data supporting the pathway of targeting \u03b1-globin as a treatment for \u03b2-thalassaemia. It also presents the progress of epigenetic drug and genome editing approaches currently in development to treat \u03b2-thalassaemia.<\/jats:p>","DOI":"10.3389\/fgeed.2021.752278","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T07:51:41Z","timestamp":1632988301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Genetic and Epigenetic Therapies for \u03b2-Thalassaemia by Altering the Expression of \u03b1-Globin Gene"],"prefix":"10.3389","volume":"3","author":[{"given":"Sachith","family":"Mettananda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.02.028","article-title":"Oxidative Status in the \u03b2-thalassemia Syndromes in Sri Lanka; a Cross-Sectional Survey","author":"Allen","year":"2021","journal-title":"Free Radic. 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