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

B. S. Pace, X. Qian, S. F. Ofori-Acquah

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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)
Issue number1
StatePublished - Feb 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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