Hydrodynamic delivery of plasmid DNA encoding human FcYR-Ig dimers blocks immune-complex mediated inflammation in miceGene therapy
AbstractTherapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human FcY receptor-Ig fusion molecules (FcYR-Igs) in mice by administering FcYR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcYR-Igs (CD16 A-F-Ig, CD32AR-Ig and CD32AH-Ig) reached a maximum of 130 µg ml-1 of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcYR-Igs was found to be 9-16 days and western blot analysis showed that the FcÎ³R-Igs were expressed as a homodimer. The hydrodynamically expressed FcYR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcYR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcYR-Ig gene can be used to study the consequences of blocking IC binding to FcYRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.
Citation InformationRangaiah Shashidharamurthy, D. Machiah, Erica N. Bozeman, S. Srivatsan, et al.. "Hydrodynamic delivery of plasmid DNA encoding human FcYR-Ig dimers blocks immune-complex mediated inflammation in mice" Gene therapy Vol. 19 Iss. 9 (2012) p. 877 - 885
Available at: http://works.bepress.com/rangaiah_shashidharamurthy/25/