Selective inhibition of beta-globin RNA transcripts by antisense RNA molecules.

Betty Sue Pace, X. Qian, S. F. Ofori-Acquah

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Inhibition of beta-globin gene expression by antisense nucleic acids is a potentially powerful therapeutic strategy for sickle cell disease. To develop clinically relevant beta-globin antisense agents we created nine stable mouse erythroleukemia cell lines expressing unique anti-beta-globin RNA transcripts with different potentials for cross-hybridization with gamma-globin mRNA. We observed variable inhibition of beta-globin expression independent of the hybridization potential of the respective antisense beta-globin RNA transcript. Similarly, inhibition of gamma-globin expression by anti-beta transcripts varied widely in the nine stable cell lines. Three neighboring regions in the beta-globin gene with low RNA folding potentials conferred significantly stronger antisense effect toward beta-globin while sparing the homologous targets in gamma-globin. We have identified for the first time targets in the beta-globin gene for which the homologous regions in gamma-globin are relatively inaccessible to antisense attack. Our findings offer the prospect of using this approach to reduce the proportion of intracellular hemoglobin S. Gene therapy strategies which combine gamma-globin induction along with beta-globin inhibition using antisense vectors may yield more favorable anti-sickling effects longterm.

Original languageEnglish (US)
Pages (from-to)43-51
Number of pages9
JournalCellular and molecular biology (Noisy-le-Grand, France)
Volume50
Issue number1
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Antisense RNA
beta-Globins
gamma-Globins
RNA
Molecules
Genes
Cells
RNA Folding
Sickle Hemoglobin
Cell Line
Gene therapy
Leukemia, Erythroblastic, Acute
Sickle Cell Anemia
Gene expression
Genetic Therapy
Nucleic Acids
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Selective inhibition of beta-globin RNA transcripts by antisense RNA molecules. / Pace, Betty Sue; Qian, X.; Ofori-Acquah, S. F.

In: Cellular and molecular biology (Noisy-le-Grand, France), Vol. 50, No. 1, 01.01.2004, p. 43-51.

Research output: Contribution to journalArticle

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