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Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells.
- Source :
-
International journal of molecular medicine [Int J Mol Med] 2015 Jan; Vol. 35 (1), pp. 51-8. Date of Electronic Publication: 2014 Nov 14. - Publication Year :
- 2015
-
Abstract
- In the treatment of hemoglobinopathies, amending altered hemoglobins and/or globins produced in excess is an important part of therapeutic strategies and the selective inhibition of globin production may be clinically beneficial. Therefore the development of drug-based methods for the selective inhibition of globin accumulation is required. In this study, we employed peptide nucleic acids (PNAs) to alter globin gene expression. The main conclusion of the present study was that PNAs designed to target adult murine β-globin mRNA inhibit hemoglobin accumulation and erythroid differentiation of murine erythroleukemia (MEL) cells with high efficiency and fair selectivity. No major effects were observed on cell proliferation. Our study supports the concept that PNAs may be used to target mRNAs that, similar to globin mRNAs, are expressed at very high levels in differentiating erythroid cells. Our data suggest that PNAs inhibit the excess production of globins involved in the pathophysiology of hemoglobinopathies.
- Subjects :
- Animals
Cell Differentiation drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Humans
K562 Cells
Mice
Nucleic Acid Conformation
Peptide Nucleic Acids chemical synthesis
Peptide Nucleic Acids chemistry
RNA, Messenger chemistry
Hemoglobins biosynthesis
Leukemia, Erythroblastic, Acute genetics
Leukemia, Erythroblastic, Acute metabolism
Peptide Nucleic Acids pharmacology
RNA, Messenger genetics
beta-Globins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-244X
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25405921
- Full Text :
- https://doi.org/10.3892/ijmm.2014.2005