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Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis.

Publication ,  Journal Article
Fisher, AA; Ye, D; Sergueev, DS; Fisher, MH; Shaw, BR; Juliano, RL
Published in: The Journal of biological chemistry
June 2002

Antisense oligonucleotides are potentially powerful tools for selective control of cellular and viral gene expression. Crucial to successful application of this approach is the specificity of the oligonucleotide for the chosen RNA target. Here we apply DNA array technology to examine the specificity of antisense oligonucleotide treatments. The molecules used in these studies consisted of phosphorothioate oligomers linked to the Antennapedia (Ant) delivery peptide. The antisense oligonucleotide component was complementary to a site flanking the AUG of the MDR1 message, which codes for P-glycoprotein, a membrane ATPase associated with multidrug resistance in tumor cells. Using a DNA array of 2059 genes, we analyzed cellular responses to molecules comprised of Ant peptide-oligonucleotide conjugates, as well as to the Ant peptide alone. Besides the expected reduction in MDR1 message level, 37 other genes (approximately 2% of those tested) showed changes of comparable magnitude. The validity of the array results was confirmed for selected genes using Northern blots to assess messenger RNA levels. These results suggest that studies using antisense oligonucleotide technology to modulate gene expression need to be interpreted with caution.

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Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

June 2002

Volume

277

Issue

25

Start / End Page

22980 / 22984

Related Subject Headings

  • Tumor Cells, Cultured
  • RNA
  • Protein Binding
  • Peptides
  • Oligonucleotides, Antisense
  • Oligonucleotide Array Sequence Analysis
  • Molecular Sequence Data
  • Humans
  • Flow Cytometry
  • Down-Regulation
 

Citation

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Fisher, A. A., Ye, D., Sergueev, D. S., Fisher, M. H., Shaw, B. R., & Juliano, R. L. (2002). Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis. The Journal of Biological Chemistry, 277(25), 22980–22984. https://doi.org/10.1074/jbc.m203347200
Fisher, Anna Astriab, Dongjiu Ye, Dimitri S. Sergueev, Michael H. Fisher, Barbara Ramsay Shaw, and Rudolph L. Juliano. “Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis.The Journal of Biological Chemistry 277, no. 25 (June 2002): 22980–84. https://doi.org/10.1074/jbc.m203347200.
Fisher AA, Ye D, Sergueev DS, Fisher MH, Shaw BR, Juliano RL. Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis. The Journal of biological chemistry. 2002 Jun;277(25):22980–4.
Fisher, Anna Astriab, et al. “Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis.The Journal of Biological Chemistry, vol. 277, no. 25, June 2002, pp. 22980–84. Epmc, doi:10.1074/jbc.m203347200.
Fisher AA, Ye D, Sergueev DS, Fisher MH, Shaw BR, Juliano RL. Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis. The Journal of biological chemistry. 2002 Jun;277(25):22980–22984.

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

June 2002

Volume

277

Issue

25

Start / End Page

22980 / 22984

Related Subject Headings

  • Tumor Cells, Cultured
  • RNA
  • Protein Binding
  • Peptides
  • Oligonucleotides, Antisense
  • Oligonucleotide Array Sequence Analysis
  • Molecular Sequence Data
  • Humans
  • Flow Cytometry
  • Down-Regulation