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End date: 2019 × Start date: 2017 × DDC: 540 × DDC: 610 × WGL Institute: INM ×

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    Kinetics of mRNA delivery and protein translation in dendritic cells using lipid-coated PLGA nanoparticles
    (London : Biomed Central, 2018) Yasar, Hanzey; Biehl, Alexander; De Rossi, Chiara; Koch, Marcus; Murgia, Xabi; Loretz, Brigitta; Lehr, Claus-Michael
    Background: Messenger RNA (mRNA) has gained remarkable attention as an alternative to DNA-based therapies in biomedical research. A variety of biodegradable nanoparticles (NPs) has been developed including lipid-based and polymer-based systems for mRNA delivery. However, both systems still lack in achieving an efficient transfection rate and a detailed understanding of the mRNA transgene expression kinetics. Therefore, quantitative analysis of the time-dependent translation behavior would provide a better understanding of mRNA's transient nature and further aid the enhancement of appropriate carriers with the perspective to generate future precision nanomedicines with quick response to treat various diseases. Results: A lipid-polymer hybrid system complexed with mRNA was evaluated regarding its efficiency to transfect dendritic cells (DCs) by simultaneous live cell video imaging of both particle uptake and reporter gene expression. We prepared and optimized NPs consisting of poly (lactid-co-glycolid) (PLGA) coated with the cationic lipid 1, 2-di-O-octadecenyl-3-trimethylammonium propane abbreviated as LPNs. An earlier developed polymer-based delivery system (chitosan-PLGA NPs) served for comparison. Both NPs types were complexed with mRNA-mCherry at various ratios. While cellular uptake and toxicity of either NPs was comparable, LPNs showed a significantly higher transfection efficiency of ~ 80% while chitosan-PLGA NPs revealed only ~ 5%. Further kinetic analysis elicited a start of protein translation after 1 h, with a maximum after 4 h and drop of transgene expression after 48 h post-transfection, in agreement with the transient nature of mRNA. Conclusions: Charge-mediated complexation of mRNA to NPs enables efficient and fast cellular delivery and subsequent protein translation. While cellular uptake of both NP types was comparable, mRNA transgene expression was superior to polymer-based NPs when delivered by lipid-polymer NPs.
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    Neurodynamic evaluation of hearing aid features using EEG correlates of listening effort
    (Dordrecht : Springer, 2017) Bernarding, Corinna; Strauss, Daniel J.; Hannemann, Ronny; Seidler, Harald; Corona-Strauss, Farah I.
    In this study, we propose a novel estimate of listening effort using electroencephalographic data. This method is a translation of our past findings, gained from the evoked electroencephalographic activity, to the oscillatory EEG activity. To test this technique, electroencephalographic data from experienced hearing aid users with moderate hearing loss were recorded, wearing hearing aids. The investigated hearing aid settings were: a directional microphone combined with a noise reduction algorithm in a medium and a strong setting, the noise reduction setting turned off, and a setting using omnidirectional microphones without any noise reduction. The results suggest that the electroencephalographic estimate of listening effort seems to be a useful tool to map the exerted effort of the participants. In addition, the results indicate that a directional processing mode can reduce the listening effort in multitalker listening situations.