Induction of Fetal Hemoglobin In Vivo Mediated by a Synthetic γ-Globin Zinc Finger Activator
Joint Authors
de Los Rios, Johana Bravo
Barbas, Carlos F.
Peterson, Kenneth R.
Costa, Flávia C.
Fedosyuk, Halyna
Neades, Renee
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-15
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Sickle cell disease (SCD) and β-thalassemia patients are phenotypically normal if they carry compensatory hereditary persistence of fetal hemoglobin (HPFH) mutations that result in increased levels of fetal hemoglobin (HbF, γ-globin chains) in adulthood.
Thus, research has focused on manipulating the reactivation of γ-globin gene expression during adult definitive erythropoiesis as the most promising therapy to treat these hemoglobinopathies.
Artificial transcription factors (ATFs) are synthetic proteins designed to bind at a specific DNA sequence and modulate gene expression.
The artificial zinc finger gg1-VP64 was designed to target the −117 region of the Aγ-globin gene proximal promoter and activate expression of this gene.
Previous studies demonstrated that HbF levels were increased in murine chemical inducer of dimerization (CID)-dependent bone marrow cells carrying a human β-globin locus yeast artificial chromosome (β-YAC) transgene and in CD34+ erythroid progenitor cells from normal donors and β-thalassemia patients.
Herein, we report that gg1-VP64 increased γ-globin gene expression in vivo, in peripheral blood samples from gg1-VP64 β-YAC double-transgenic (bigenic) mice.
Our results demonstrate that ATFs function in an animal model to increase gene expression.
Thus, this class of reagent may be an effective gene therapy for treatment of some inherited diseases.
American Psychological Association (APA)
Costa, Flávia C.& Fedosyuk, Halyna& Neades, Renee& de Los Rios, Johana Bravo& Barbas, Carlos F.& Peterson, Kenneth R.. 2012. Induction of Fetal Hemoglobin In Vivo Mediated by a Synthetic γ-Globin Zinc Finger Activator. Anemia،Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-477183
Modern Language Association (MLA)
Costa, Flávia C.…[et al.]. Induction of Fetal Hemoglobin In Vivo Mediated by a Synthetic γ-Globin Zinc Finger Activator. Anemia No. 2012 (2012), pp.1-8.
https://search.emarefa.net/detail/BIM-477183
American Medical Association (AMA)
Costa, Flávia C.& Fedosyuk, Halyna& Neades, Renee& de Los Rios, Johana Bravo& Barbas, Carlos F.& Peterson, Kenneth R.. Induction of Fetal Hemoglobin In Vivo Mediated by a Synthetic γ-Globin Zinc Finger Activator. Anemia. 2012. Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-477183
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-477183