又一成功案例！NEJM：BCL11A转录后基因沉默治疗镰状细胞病疗 …
2020年12月18日 · bcl11a是成人红细胞中γ珠蛋白表达和hbf产生的抑制因子，它的下调是诱导hbf的有潜力的治疗策略。 2020年12月5日，美国哈佛医学院David A. Williams团队在《NEJM》上在线发表了一篇题为“Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease”的文章，研究了BCL11A ...
Targeted deletion of BCL11A gene by CRISPR-Cas9 system for ... - PubMed
2019年7月5日 · In our study, deletion of 200bp of BCL11A erythroid enhancer including GATAA motif leads to strong induction of γ-hemoglobin expression in K562 cells, but not in KU-812 and KG-1 cells. Altogether, our findings highlight the therapeutic potential of CRISPR-Cas9 as a precision genome editing tool for treating β-thalassemia.
Fetal Hemoglobin (HbF) Silencer BCL11A Acts through a Novel …
2017年12月7日 · Genome-wide association studies led to identification of the regulatory factor BCL11A, which is a major contributor to HbF silencing. Despite clear evidence for its involvement, how BCL11A acts to repress gamma-globin gene expression has remained unknown.
Identification Of BCL11A Structure-Function Domains For Fetal ...
2013年11月15日 · Reactivation of fetal hemoglobin (HbF, α 2γ2) expression in adults ameliorates the clinical symptoms in patients with the major β-hemoglobin disorders, sickle cell disease (SCD) and β-thalassemias. The zinc-finger protein BCL11A is a major modulator of hemoglobin switching and HbF silencing.
CRISPR–Cas9-mediated gene editing of the - Nature
2022年8月4日 · Gene editing to disrupt the GATA1-binding site at the +58 BCL11A erythroid enhancer could induce γ-globin expression, which is a promising therapeutic strategy to alleviate β-hemoglobinopathy...
Pathogenic BCL11A variants provide insights into the …
2021年10月11日 · Our analysis of missense variants causing loss-of-function in vivo illuminates mechanisms by which BCL11A silences HbF and also suggests potential therapeutic avenues for HbF induction to treat sickle cell disease and β-thalassemia.
Comparative targeting analysis of KLF1, BCL11A, and HBG1/2 in
2020年6月23日 · Several preclinical and clinical studies have been performed in order to induce HbF by knocking-down genes involved in HbF repression (KLF1 and BCL11A) or disrupting the binding sites of...
BCL11A转录后基因沉默治疗镰状细胞病疗效显著 - 科学网
2020年12月5日 · This study validates BCL11A inhibition as an effective target for HbF induction and provides preliminary evidence that shmiR-based gene knockdown offers a favorable risk–benefit profile in ...
Transcriptional silencing of fetal hemoglobin by BCL11A
As a factor critical for gamma-globin gene silencing, BCL11A should be considered as a therapeutic target to increase HbF in a directed manner in beta-thalassemia patients. The beta-thalassemia syndromes are a major global health problem. Increased levels of fetal hemoglobin (HbF) ameliorate the clinical symptoms seen in this disease.
The LRF/ZBTB7A Transcription Factor Is a BCL11A-Independent …
2015年12月3日 · ZBTB7A Δ/Δ cells exhibited HbF levels greater than 60%, while that of parental cells was less than 3%. Notably, the HbF reactivation occurred without changes in levels of transcripts encoding known HbF repressors, including …