Hydrodynamic delivery of plasmid DNA encoding human FcYR-Ig dimers blocks immune-complex mediated inflammation in mice

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Therapeutic 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 FcγR-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.

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Gene therapy





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This article was published in Gene therapy, Volume 19, Issue 9, Pages 877-885.

The published version is available at http://dx.doi.org/10.1038/gt.2011.175.

Copyright © 2012 Nature Publishing Group.

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