Regulation of gene expression with double-stranded phosphorothioate oligonucleotides

Anna Bielinska, Ramesh A. Shivdasani, Liquan Zhang, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or κB consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-κB. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-κB-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the EL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects.

Original languageEnglish (US)
Pages (from-to)997-1000
Number of pages4
JournalScience
Volume250
Issue number4983
StatePublished - Nov 16 1990
Externally publishedYes

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Phosphorothioate Oligonucleotides
Gene Expression Regulation
Oligonucleotides
Octamer Transcription Factors
T-Cell Leukemia
Consensus Sequence
DNA-Binding Proteins
Therapeutic Uses
Immunosuppressive Agents
Interleukin-2
Proteins
Plasmids
B-Lymphocytes
Transcription Factors
HIV
Gene Expression
Cell Line
Genes

ASJC Scopus subject areas

  • General

Cite this

Bielinska, A., Shivdasani, R. A., Zhang, L., & Nabel, G. J. (1990). Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science, 250(4983), 997-1000.

Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. / Bielinska, Anna; Shivdasani, Ramesh A.; Zhang, Liquan; Nabel, Gary J.

In: Science, Vol. 250, No. 4983, 16.11.1990, p. 997-1000.

Research output: Contribution to journalArticle

Bielinska, A, Shivdasani, RA, Zhang, L & Nabel, GJ 1990, 'Regulation of gene expression with double-stranded phosphorothioate oligonucleotides', Science, vol. 250, no. 4983, pp. 997-1000.
Bielinska A, Shivdasani RA, Zhang L, Nabel GJ. Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science. 1990 Nov 16;250(4983):997-1000.
Bielinska, Anna ; Shivdasani, Ramesh A. ; Zhang, Liquan ; Nabel, Gary J. / Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. In: Science. 1990 ; Vol. 250, No. 4983. pp. 997-1000.
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