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KMID : 0545120000100050707
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Journal of Microbiology and Biotechnology
2000 Volume.10 No. 5 p.707 ~ p.713
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In vitro Selection of the 2´-Fluoro-2´-Deoxyribonucleotide Decoy RNA Inhibitor of Myasthenic Autoantibodies
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Seo Hwa-Seon
Lee Seong-Wook
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Abstract
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Myasthenia gravis (MG) is caused mainly by autoantibodies directed against acetylcholine receptors located in the postsynaptic muscle cell membrane. Using in vitro selection techniques, we isolated an RNA containing 2´-fluoro pyrimidines that can specifically and avidly (K_d∼25nM) bind rat monoclonal antibody called mAb198, which recognizes the main immunogenic region on the acetylcholine receptors. This RNA can act as a very effective decoy and block mAb198 binding to the receptors in vitro. Furthermore, this RNA decoy can prevent the antigenic modulation of the acetylcholine receptor caused by mAb198 in human muscle cell cultures with an IC_50 of approximately 2.4μM. These results indicate that the RNA selected in this study is a more potent decoy inhibitor of myasthenic antibodies than the previously identified RNA with 2´-amino pyrimidines [11]. Moreover, this RNA cross-reacts with autoantibodies from patients with MG and can protect human cells from the effects of these antibodies. These observations have important implications for developing an antigen-specific treatment of autoimmune diseases including MG, which is based on decoy RNAs selected in vitro.
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KEYWORD
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