The Journal of Experimental Medicine
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Journal of Experimental Medicine, Vol 184, 315-324, Copyright © 1996 by Rockefeller University Press

ARTICLES

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

SW Lee and BA Sullenger
Department of Experimental Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.

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.
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