Expression kinetics and innate immune response after electroporation and lipid nanoparticle mediated delivery of a self-amplifying mRNA in the skin of mice

In this work we studied the expression kinetics and innate immune response of a self-amplifying mRNA (sa-RNA) after electroporation and lipid nanoparticle (LNP) mediated delivery in the skin of mice. Intradermal electroporation of the sa-RNA resulted in a plateau-shaped expression with the plateau between day 3 and 10. The overall protein expression of sa-RNA was significant higher than that obtained after electroporation of pDNA or non-replication mRNAs. Moreover, intradermal electroporation of sa-RNA induced a short-lived innate immune response that did not affect the expression of the sa-RNA. A complete different expression profile and innate immune response was observed when LNPs were used. The expression peaked 24h after intradermal injection of sa-RNA-LNPs and subsequently showed a sharp drop. This drop can be explained by the strong innate immune response elicited by the sa-RNA-LNPs 4h after injection. Interestingly, sa-RNA-LNPs were able to transfection the draining lymph nodes after intradermal injection. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=59 SRC="FIGDIR/small/528612v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@fcbbb9org.highwire.dtl.DTLVardef@889a46org.highwire.dtl.DTLVardef@48784corg.highwire.dtl.DTLVardef@1d1ecb4_HPS_FORMAT_FIGEXP M_FIG C_FIG