Precise correction of a spectrum of beta-thalassaemic mutations in the coding and non-coding regions by base editors

Engineered erythroid model harbouring spectrum of beta-thalassemia point-mutations spanning multiple regions of the HBB-gene, including promoter, intron and exon for primary screening of BEs and sgRNA. The identified potential sgRNAs from primary screening were re-evaluated in created beta-thalassemia cellular model along with its off-target effects. Further, performed HbE correction in severe beta-thalassemic patients derived HSPCs which led to functional restoration of adult hemoglobin.Off-target NGS data of Initiation-codon (ATG>ACG), IVS2-849(A>G) and HbE(GAG>AAG) in created HUDEP-2 cellular model after correction using base editors and patients HSPCs edited NGS data.