2021年6月2日 · These findings point towards a one-time autologous treatment for SCD that eliminates pathogenic HBB S, generates benign HBB G, and minimizes the undesired consequences of double-strand DNA...

2023年4月17日 · Sickle-cell disease (SCD) is caused by an A·T-to-T·A transversion mutation in the β -globin gene (HBB). Here we show that prime editing can correct the SCD allele...

2024年6月11日 · Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. SCD is characterized by mutations in the HBB gene, which encodes the β subunit of...

2021年6月3日 · 镰状细胞病（SCD），是一种常染色体隐型遗传病，是由表达β-珠蛋白的HBB基因突变引起，突变导致β-珠蛋白上第六位原本的谷氨酸被替换成缬氨酸，进而导致红细胞形态异常，呈现镰刀型，因此也叫做镰刀状细胞贫血症。 镰状细胞病患者会出现包括贫血、严重急性和慢性疼痛、免疫缺陷、多器官衰竭，甚至早逝。 骨髓移植是根治这种遗传疾病的方法，然而，骨髓移植费用巨大、配型极其困难，因此，绝大多数患者只能依赖频繁输血维持生命，不仅给家庭带来 …

2020年4月15日 · SCD is caused by a point mutation in human β-globin gene (HBB). Clinical strategies have demonstrated substantial success, however there is not any permanent cure for SCD available. CRISPR/Cas9 platform uses a single endonuclease and a single guide RNA (gRNA) to induce sequence-specific DNA double strand break (DSB).

Ex vivo delivery of mRNA encoding base editor with a targeting guide RNA into hematopoietic stem and progenitor cells (HSPCs) from SCD patients resulted in 80% HBB S-to-HBB G conversion. Sixteen weeks after transplantation of edited human HSPCs into immunodeficient mice, HBB G frequency was 68% and bone marrow reticulocytes demonstrated a 5 ...

2021年6月15日 · Sickle cell disease (SCD) is a genetic disorder caused by a mutation in both copies of a person’s HBB gene. This gene encodes a component of hemoglobin, the oxygen-carrying protein in red blood cells. The mutation causes hemoglobin molecules to stick together, creating sickle-shaped red blood cells.

4 天之前 · β-globinopathies, comprising mainly sickle cell disease (SCD) and β-thalassemia, remain the most attractive target for gene-editing approaches, as they affect millions. SCD is caused by a point mutation in the β-globin (HBB) gene, resulting in a defective hemoglobin that polymerizes and sickles red blood cells (RBCs). β-thalassemia is caused by a mutant β-globin gene (over 200 different ...

Homozygosity (HbSS) is the most common genotype, resulting in sickle cell anemia (SCA), which is the most severe in the sickle cell disease (SCD) spectrum. Other forms are compound heterozygotes of HbS with other abnormal ß-chain variants, e.g., HbSC and HbSβ-thal.

Base editing of human HSPCs avoided the p53 activation and larger deletions that have been observed following Cas9 nuclease treatment. These findings point towards a one-time autologous treatment for SCD that eliminates pathogenic HBB S, generates benign HBB G, and minimizes the undesired consequences of double-strand DNA breaks.