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DC Field | Value | Language |
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dc.contributor.author | Badat, M. | - |
dc.contributor.author | Ejaz, A. | - |
dc.contributor.author | Hua, P. | - |
dc.contributor.author | Rice, S. | - |
dc.contributor.author | Zhang, W. | - |
dc.contributor.author | Hentges, L.D. | - |
dc.contributor.author | Fisher, C.A. | - |
dc.contributor.author | Denny, N. | - |
dc.contributor.author | Schwessinger, R. | - |
dc.contributor.author | Yasara, N. | - |
dc.contributor.author | Roy, N.B.A. | - |
dc.contributor.author | Issa, F. | - |
dc.contributor.author | Roy, A. | - |
dc.contributor.author | Telfer, P. | - |
dc.contributor.author | Hughes, J. | - |
dc.contributor.author | Mettananda, S. | - |
dc.contributor.author | Higgs, D.R. | - |
dc.contributor.author | Davies, J.O.J. | - |
dc.date.accessioned | 2023-04-27T06:01:15Z | - |
dc.date.available | 2023-04-27T06:01:15Z | - |
dc.date.issued | 2023 | - |
dc.identifier.citation | Nature Communications.2023;14(1):2238. | en_US |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://repository.kln.ac.lk/handle/123456789/26124 | - |
dc.description | indexed in MEDLINE. | en_US |
dc.description.abstract | Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE β-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any mutation causing severe β-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (β-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 90% in primary human CD34 + cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Nature Pub. Group | en_US |
dc.subject | β-thalassaemia | en_US |
dc.subject | Haemoglobin | en_US |
dc.title | Direct correction of haemoglobin E β-thalassaemia using base editors | en_US |
dc.type | Article | en_US |
Appears in Collections: | Journal/Magazine Articles |
Files in This Item:
File | Description | Size | Format | |
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41467_2023_Article_37604.pdf | 1.66 MB | Adobe PDF | View/Open |
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