Therapeutic effect of galactosyltransferase- and sialyltransferase-encoding mRNA in rheumatoid arthritis.

Glycoengineering of IgG, particularly Fc glycosylation, holds significant promise for treating autoimmune diseases by modulating antibody effector functions. However, methods that precisely control IgG glycosylation profiles in vivo are still lacking. In this study, by delivering mRNAs encoding the glycosyltransferases B4GALT1 and ST6GAL1 intravenously, we successfully expressed functional enzymes and demonstrated therapeutic benefits in rheumatoid arthritis animal models in a platelet-dependent manner. We further verified that intra-articular administration effectively ameliorated collagen-induced arthritis in rats. Our findings demonstrate that IgG galactosylation and sialylation, modulated by mRNA drug technology, shift immune responses from pro-inflammatory to anti-inflammatory states, similar to the mechanisms of intravenous immunoglobulin (IVIG) therapies. This study establishes glycosyltransferase-encoding mRNA-LNP technology as a versatile platform for modulating in vivo IgG glycosylation and treating associated diseases.