Treatment of Experimental Autoimmune Encephalomyelitis with Lipid Nanoparticles Loaded with siRNA Targeting Neogenin

Abstract

Multiple sclerosis (MS) develops due to an abnormal T-cell immune response to autoantigens and control of T-cell activation is a mainstream approach for its treatment. In the present study, neogenin, a key molecule for T-cell activation, was used as a targeted molecular gene therapy for MS. Lipid nanoparticles (LNPs) loaded with small interfering RNA (siRNA) targeting neogenin (LNPsiNeo) were prepared, and their therapeutic effect on experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein, a model of MS was evaluated. Neogenin gene expression was reduced by LNPsiNeo in mouse EL-4 cells and splenocytes of LNPsiNeo-treated EAE mouse. Additionally, fluorescence-activated cell sorting (FACS) revealed that the number of CD4⁺ T cells in the splenocytes of EAE mouse decreased after intravenous injection of LNPsiNeo. Furthermore, the progression of encephalomyelitis symptoms was significantly suppressed by LNPsiNeo, whereas the lipid nanoparticle with control siRNA failed to show any effect. The present study suggests that neogenin is a target molecule for EAE gene therapy and LNPsiNeo may be suitable for the MS treatment.