Ja. Doudna et al., SELECTION OF AN RNA MOLECULE THAT MIMICS A MAJOR AUTOANTIGENIC EPITOPE OF HUMAN INSULIN-RECEPTOR, Proceedings of the National Academy of Sciences of the United Statesof America, 92(6), 1995, pp. 2355-2359
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 spe
cifically to autoantibodies and inhibit their interaction with the tar
get antigen. Here we report the identification of an RNA sequence that
binds a mouse monoclonal antibody specific for an autoantigenic epito
pe of human insulin receptor. The RNA ligand binds specifically and wi
th high affinity (apparent Kd similar or equal to 2 nM) to the anti-in
sulin receptor antibody and not to other mouse IgGs. The RNA can also
act as a decoy, blocking the antibody from binding the insulin recepto
r. Thus, it probably binds near the combining site on the antibody. St
rikingly, the RNA cross-reacts with autoantibodies from patients with
extreme insulin resistance. One simple explanation is that the selecte
d RNA may structurally mimic the antigenic epitope on the insulin rece
ptor protein. These results suggest that decoy RNAs may be useful in t
he treatment of autoimmune diseases.