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bioRxiv · 10.1101/528612

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

Huysmans, H.·Zhong, Z.·De Temmerman, J.·Mui, B. L.·Tam, Y. K.·Mc Cafferty, S.·Gitsels, A.·Vanrompay, D.·Sanders, N.
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Abstract

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

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Huysmans, H., Zhong, Z., De Temmerman, J., Mui, B. L., Tam, Y. K., Mc Cafferty, S., Gitsels, A., Vanrompay, D., Sanders, N.. 2019-01-23. Expression kinetics and innate immune response after electroporation and lipid nanoparticle mediated delivery of a self-amplifying mRNA in the skin of mice. https://doi.org/10.1101/528612

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