Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine receptors from myasthenic antibodies.
The muscular weakness and fatigability associated with myasthenia gravis are engendered by autoantibodies directed against acetylcholine receptors on muscle cells at neuromuscular junctions. The pathogenic consequences of this immune response can potentially be modulated by molecules that bind such autoantibodies and block their interaction with these receptors. We report the isolation of a small nuclease-resistant RNA molecule that binds both a rat monoclonal antibody that recognizes the main immunogenic region on the acetylcholine receptor, and autoantibodies from patients with myasthenia gravis. Moreover, this RNA can act as a decoy and protect acetylcholine receptors on human cells from the effects of these antibodies.
Lee
S W
SW
Department of Experimental Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Sullenger
B A
BA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000187:drug effects / Q000378:metabolism; D001323:Autoantibodies / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular / Q000379:methods; D015536:Down-Regulation / Q000187:drug effects; D000939:Epitopes; D006801:Humans; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D012313:RNA / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012260:Ribonucleases / Q000378:metabolism*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D011950:Receptors, Cholinergic; D012313:RNA; D012260:Ribonucleases