miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction
نویسندگان
چکیده
منابع مشابه
Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype.
Reducing expression of the fetal hemoglobin (HbF) repressor BCL11A leads to a simultaneous increase in γ-globin expression and reduction in β-globin expression. Thus, there is interest in targeting BCL11A as a treatment for β-hemoglobinopathies, including sickle cell disease (SCD) and β-thalassemia. Here, we found that using optimized shRNAs embedded within an miRNA (shRNAmiR) architecture to a...
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Legumain (LGMN) is highly expressed in breast cancer (BC) and other solid tumors and is a potential anticancer target. Here we investigate the anti-tumor effects of short hairpin RNAs (shRNAs) targeting LGMN embedded in a microRNA-155 (miR-155) architecture, which is driven by a radiation-inducible chimeric RNA polymerase II (Pol II) promoter. Lentiviral vectors were generated with the chimeric...
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We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were deli...
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hemoglobin f (hbf, α 2 γ 2 ) is a major contributor to the clinical heterogeneity and ameliorating agent observed in patients with the β-globin disorders including β-thalassemia and sickle cell disease (scd). during fetal life, hbf is the major hemoglobin but is largely substituted by adult hemoglobin (hba, α 2 β 2 ) following a globin expression switch after birth. increased γ-globin expressio...
متن کاملHeritable and Lineage-Specific Gene Knockdown in Zebrafish Embryo
BACKGROUND Reduced expression of developmentally important genes and tumor suppressors due to haploinsufficiency or epigenetic suppression has been shown to contribute to the pathogenesis of various malignancies. However, methodology that allows spatio-temporally knockdown of gene expression in various model organisms such as zebrafish has not been well established, which largely limits the pot...
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ژورنال
عنوان ژورنال: Molecular Therapy
سال: 2015
ISSN: 1525-0016
DOI: 10.1038/mt.2015.113