破坏BCL11A基因内含子2内的红细胞特异性增强子,可以导致红细胞特异性BCL11A抑制,该转录因子在其他造血谱系中具有多效性,这表明该位点和可能成为一处极具潜力的遗传干预靶点。 近期,来自美国国立卫生研究院的Daniel E. Bauer和John F. Ti...
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature. 2015;527(7577):192–7. : 10.1038/nature15521 .M. C. Canver, E. C. Smith, F. Sher, L. Pinello, N. E. Sanjana and O. Shalem, et al. BCL11A enhancer dissection by Cas9-mediated in situ ...
2022年8月4日,中南大学付斌,华东师范大学吴宇轩,刘明耀和李大力共同通讯在Nature Medicine 在线发表题为“CRISPR–Cas9-mediated gene editing of the BCL11A enhancer for pediatric β0/β0 transfusion-dependent β-thalassemia”的研究论文,该研究报告了一项正在进行的 1/2 期试验 (NCT04211480) 的初步结果,该试...
Previously we identified an erythroid enhancer ofBCL11A, subject to common genetic variation associated with fetal hemoglobin (HbF) level, whose mouse ortholog is necessary for erythroid BCL11A expression. Here we develop pooled CRISPR-Cas9 guide RNA libraries to performin situsaturating mutagenesis of...
Figure 1.The BCL11A–HbF repression axis. BCL11A itself relies on an erythroid enhancer, the subject of common trait-associated genetic variation, for its adult-stage erythroid expression pattern. GATA1 and TAL1 bind to this enhancer, and KLF1 (which may in turn be regulated by MYB) transact...
We transplanted BCL11A enhancer-edited, autologous, hematopoietic stem and progenitor cells into two children, one carrying the β0/β0 genotype, classified as the most severe type of TDT. Primary endpoints included engraftment, overall survival and incidence of adverse events (AEs). Both patients ...
bcl11a+62位的碱基序列(参见序列seq id no:14)位于人类第二号染色体的第60,717,492至60,718,860的区域(相对于人hg19基因组)(参见参见erythroid enhancer of bcl11a subject to genetic variation determines fetal hemoglobin level,daniel e.bauer et al.,science,vol.342,supplementary material)。这些区域被编辑...
18,19,20,21,22,23 Emerging evidence indicates that BCL11A knockdown may lead to HSC impairment, as observed in competitive transplantations,29 thus the erythroid-specific BCL11A enhancer might constitute a more suitable clinical target.24,30 Nevertheless, the main focus of this study was not to...
Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci U S A. 1997;94:569–74. Article CAS PubMed Central PubMed Google Scholar Karsunky H, Zeng H, Schmidt T, Zevnik B, Kluge R, ...
Hematopoietic stem cells (HSCs) are a rare cell type with the ability of long-term self-renewal and multipotency to reconstitute all blood lineages. HSCs are typically purified from the bone marrow using cell surface markers. Recent studies have identifi