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National Repository of Grey Literature 1 records found  Search took 0.01 seconds. 
Immune stimulation by lipid nanoparticles
 Aulichová, Veronika ; Grantz Šašková, Klára (advisor) ; Pačesová, Andrea (referee)
Lipid nanoparticles are the most advanced non-viral delivery system of nucleic acids. They enable safe and efficient transport of nucleic acids to the targeted cells and represent a key enabling technology of RNA therapeutics. RNA therapeutics represent a rapidly emerging field of genetic medicine; however, due to the nature of RNA molecules and their susceptibility to nuclease degradation, the delivery system is crucial for its translation to the clinic. This thesis explores the ability of lipid nanoparticles based on the XMAN6 ionizable lipidoid to elicit an immune response against mRNA-encoded antigen. XMAN6 is a lead lipidoid from a new class of adamantane-based ionizable lipidoids developed in our team. The mRNA-LNP formulations were first tested in vitro to evaluate their functionality and cytokine production and then in vivo using a mouse model. LNPs were applied via two different routes and in different experimental set ups, and their safety was evaluated by analyzing mouse activity. The data showed that XMAN6 is a promising lipidoid for in vivo delivery of mRNA. The mRNA-LNPs successfully induced the antibody response against the encoded antigen by intraperitoneal and intramuscular application. XMAN6 LNPs showed to be suitable for in vivo use, as they were well tolerated and caused only...
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