Apr 22, 2024 · The p.Glu7Val variant (also known as p.Glu6Val or hemoglobin S variant) in HBB is a well-established variant which, in the homozygous state, causes sickle cell anemia and which accounts for 60-70% of sickle cell disease in the US (Bender 2003 PMID: 20301551, Serjeant 1968 PMID: 4232783).

Dec 8, 2017 · Here we present our IND-enabling preclinical development for CRISPR-Cas9 and rAAV6-mediated HBB genome editing of the E6V mutation in SCD-derived HSPCs as well as in plerixafor mobilized HSPCs from multiple healthy individuals.

Oct 18, 2016 · The Hb S variant (HBB: c.20A>T; p.Glu7Val, also known as Glu6Val when numbered from the mature protein, HbVar ID: 226, rs334) is a common pathogenic beta globin variant. Heterozygosity for Hb S is consistent with sickle cell trait. Homozygosity for Hb S results in sickle cell anemia.

Jan 29, 2021 · Here, we use a humanized globin-cluster SCD mouse model to study Cas9-AAV6-mediated HBB-correction in functional HSCs within the context of autologous transplantation.

Nov 5, 2024 · We believe the mechanism of the RNA Gene Writer to precisely write DNA at the single nucleotide level makes it an ideal modality to correct the sickle cell disease (SCD) causing mutation, HBB E6V, in hematopoietic stem cells (HSCs).

We used PE3 to install the HBB E6V mutation in HEK293T cells with 44% efficiency and 4.8% indels and isolated from a single prime editing experiment six HEK293T cell lines that are homozygous (triploid) for the HBB E6V allele (Supplementary Note 1).

We also show efficient correction of the SCD-causing E6V mutation in patient-derived HSPCs that after differentiation into erythrocytes, express adult β-globin (HbA) mRNA, confirming intact transcriptional regulation of edited HBB alleles.

SD is caused by one point mutation (E6V) in the β-globin protein (βS) which causes 39 polymerization of hemoglobin-containing β S chains, chronic hemolytic anemia, severe pain and other 40 acute crises, progressive end-organ dysfunction, and early mortality. 1,2 In contrast, almost 300 different

May 19, 2023 · SCD is an autosomal recessive genetic disorder caused by an A·T-to-T·A transversion (the E6V mutation) at codon 6 in the HBB gene, which produces the adult haemoglobin subunit β-globin. The...

Nov 5, 2024 · Methods: We used CRISPR editing to modify humanized Townes HbSS (HBB E6V/E6V) mice, converting one of the HBB E6V alleles to HBB E6K, generating HbSC (HBB E6V/E6K) mice.