scholarly journals Expression Kinetics and Innate Immune Response after Electroporation and LNP-Mediated Delivery of a Self-Amplifying mRNA in the Skin

2019 ◽  
Vol 17 ◽  
pp. 867-878 ◽  
Author(s):  
Hanne Huysmans ◽  
Zifu Zhong ◽  
Joyca De Temmerman ◽  
Barbara L. Mui ◽  
Ying K. Tam ◽  
...  
2019 ◽  
Author(s):  
Hanne Huysmans ◽  
Zifu Zhong ◽  
Joyca De Temmerman ◽  
Barbara L. Mui ◽  
Ying K. Tam ◽  
...  

AbstractIn 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.


2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.


Pneumologie ◽  
2013 ◽  
Vol 67 (S 01) ◽  
Author(s):  
P Pfeifer ◽  
M Voss ◽  
B Wonnenberg ◽  
M Bischoff ◽  
F Langer ◽  
...  

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