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Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes.

Publication ,  Journal Article
Lee, SW; Sullenger, BA
Published in: J Exp Med
August 1, 1996

An RNA containing 2'-amino pyrimidines has been isolated using in vitro selection techniques that specifically and avidly (apparent Kd approximately 30 nM) binds a mouse monoclonal antibody called MA20. This 2'-amino-derivatized RNA is at least 10,000-fold more stable than unmodified RNA in serum, and can act as a decoy and block MA20 binding to its natural antigen, the human insulin receptor, on lymphocytes. Furthermore, this RNA decoy can inhibit MA20-mediated downmodulation of insulin receptor expression on human lymphocytes in culture by up to 90%. Surprisingly, the decoy RNA cross-reacts with autoantibodies from patients with extreme insulin resistance and can inhibit these antiinsulin receptor antibodies from downmodulating insulin receptor expression by up to 80% without impeding insulin binding to its receptor. These results suggest that in vitro-selected decoy RNAs may be able to specifically and selectively block oligoclonal autoimmune responses to self-antigens in patients with autoimmune diseases.

Duke Scholars

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

August 1, 1996

Volume

184

Issue

2

Start / End Page

315 / 324

Location

United States

Related Subject Headings

  • Ribonucleases
  • Receptor, Insulin
  • RNA
  • Protein Binding
  • Nucleic Acid Conformation
  • Molecular Sequence Data
  • Mice
  • Lymphocytes
  • Insulin Resistance
  • Immunology
 

Citation

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MLA
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Lee, S. W., & Sullenger, B. A. (1996). Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes. J Exp Med, 184(2), 315–324. https://doi.org/10.1084/jem.184.2.315
Lee, S. W., and B. A. Sullenger. “Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes.J Exp Med 184, no. 2 (August 1, 1996): 315–24. https://doi.org/10.1084/jem.184.2.315.
Lee, S. W., and B. A. Sullenger. “Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes.J Exp Med, vol. 184, no. 2, Aug. 1996, pp. 315–24. Pubmed, doi:10.1084/jem.184.2.315.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

August 1, 1996

Volume

184

Issue

2

Start / End Page

315 / 324

Location

United States

Related Subject Headings

  • Ribonucleases
  • Receptor, Insulin
  • RNA
  • Protein Binding
  • Nucleic Acid Conformation
  • Molecular Sequence Data
  • Mice
  • Lymphocytes
  • Insulin Resistance
  • Immunology