title: Sequence and structural features of RNA aptamer against myasthenic autoantibodies.
abstract: Myasthenia gravis (MG) is mainly caused by autoantibodies to postsynaptic nicotinic acetylcholine receptors (AChRs). Previously, we isolated an RNA aptamer with 2'-amino pyrimidines that inhibited both a rat monoclonal antibody, which recognizes the main immunogenic region on the AChR, and MG patient autoantibodies from down-modulating AChRs on human cells. In this study, secondary configuration and binding motif of the aptamer were characterized, and moreover, various mutant aptamer forms were generated to figure out sequence and structure requirements of the aptamer. Then, we found that intrinsic structure formation and sequence composition of the selected RNA aptamer specific to the antibody are required for the aptamer activity to inhibit the myasthenic autoantibody-mediated destruction of cell surface AChRs. Noticeably, we identified 47-mer minimized aptamer version, which can efficiently protect cells from the effects of the autoantibodies and could be optimally applicable for MG therapy.
authors: Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin 448-701, Republic of Korea.
authors: Jung-Sun
authors: JS
authors: Cho
authors: Seong-Wook
authors: SW
authors: Lee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics* / Q000627:therapeutic use; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D045744:Cell Line, Tumor; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism; D009157:Myasthenia Gravis / Q000276:immunology / Q000628:therapy*; D009690:Nucleic Acid Conformation; D051381:Rats; D011950:Receptors, Cholinergic / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D052157:Aptamers, Nucleotide; D001323:Autoantibodies; D007155:Immunologic Factors; D011950:Receptors, Cholinergic