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Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor.

Abstract：

:Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind specifically to autoantibodies and inhibit their interaction with the target antigen. Here we report the identification of an RNA sequence that binds a mouse monoclonal antibody specific for an autoantigenic epitope of human insulin receptor. The RNA ligand binds specifically and with high affinity (apparent Kd congruent to 2 nM) to the anti-insulin receptor antibody and not to other mouse IgGs. The RNA can also act as a decoy, blocking the antibody from binding the insulin receptor. Thus, it probably binds near the combining site on the antibody. Strikingly, the RNA cross-reacts with autoantibodies from patients with extreme insulin resistance. One simple explanation is that the selected RNA may structurally mimic the antigenic epitope on the insulin receptor protein. These results suggest that decoy RNAs may be used in the treatment of autoimmune diseases.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Doudna JA,Cech TR,Sullenger BA

doi

10.1073/pnas.92.6.2355

subject

Has Abstract

pub_date

1995-03-14 00:00:00

pages

2355-9

issue

6

eissn

0027-8424

issn

1091-6490

journal_volume

92

pub_type

杂志文章

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