Therapeutic Potential of Lipid Nanoparticle-Encapsulated CD19-Targeting mRNAs in Lupus and Rheumatoid Arthritis.

Abstract

The hyperactivation of autoreactive B cells and plasma cells leads to the development of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), therefore, targeting the abnormal B cells and plasma cells might hold promise for the treatment of these refractory and relapsing diseases. This study developed lipid nanoparticle-encapsulated mRNA-encoding antibodies (mRNab-LNPs) targeting CD19, and evaluated their therapeutic efficacy in lupus and RA mice. mRNab-LNPs enabled robust production of anti-CD19 antibodies in multiple cell lines in vitro. Interestingly, intramuscular injection of mRNab-LNPs resulted in high and sustained production of anti-CD19 antibodies in mice. In particular, the numbers of CD19+ circulating B cells and tissue-resident plasma cells are significantly reduced by mRNab-LNPs in mice. As a result, mRNab-LNPs significantly reduced the histopathological changes and tissue injuries in both lupus and RA mice. Collectively, these findings demonstrate the therapeutic and translational potential of mRNab-LNPs in the treatment of SLE and RA.