Prevention of passively transferred experimental autoimmune myasthenia gravis by an in vitro selected RNA aptamer

FEBS Letters

Lee, Seong-Wook¹  Hwang, Byounghoon¹  Han, Kyungsook² 

[1] Department of Molecular Biology, Dankook University, Seoul 140-714, South Korea;School of Computer Science and Engineering, Inha University, Incheon 402-751, South Korea

关键词: Experimental autoimmune myasthenia gravis;    In vitro selection;    RNA aptamer;    Acetylcholine receptor;    Autoantibody;   

DOI  :  10.1016/S0014-5793(03)00745-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG), are mainly caused by autoantibodies directed against acetylcholine receptors (AChR) located in the postsynaptic muscle membrane. Previously, we isolated an RNA aptamer with 2′-fluoropyrimidines using in vitro selection techniques that acted as an effective decoy against both a rat monoclonal antibody called mAb198, which recognizes the main immunogenic region on the AChR, and a significant fraction of patient autoantibodies with MG. To investigate the therapeutic potential of the RNA, we tested the ability of the RNA aptamer to protect the receptors in vivo from mAb198. Clinical symptoms of EAMG in rats engendered by passive transfer of mAb198 were efficiently inhibited by a truncated RNA aptamer that was modified with polyethylene glycol, but not by control scrambled RNA. Moreover, the loss of AChR in the animals induced by the antibody was also significantly blocked with the modified RNA aptamer. These results suggested that RNA aptamers could be applied for antigen-specific treatment for autoimmune diseases including MG.

【 授权许可】

Unknown