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After intramuscular injection, lipid nanoparticle-mRNA (LNP-mRNA) vaccines are internalized by somatic cells (for example, muscle cells) and tissue-resident or recruited antigen-presenting.
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Fig. 6. Lipids used in the mRNA-LNP COVID-19 vaccines BNT162b2 (Comirnaty) and mRNA-1273. Another key aspect of LNP stability is physical degradation. There are three main types of physical instability that can occur: aggregation, fusion, and leakage of the encapsulated pharmaceutical ingredient.
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Six hours after LNP treatments, cells were lysed with Bright-Glo reagent and the relative intensity of luciferase expression was evaluated. As shown in Fig. 2A , 244C10, 245C10, and 246C10 showed substanial luciferase expression and 246C10 LNPs showed the highest luminescent expression.
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While things may have slowed down a little since the rapid approvals of the COVID-19 vaccines, the excitement around RNA-LNP is still going strong. We spoke to nanomedicine experts at Precision NanoSystems to understand the process development and manufacturing challenges that lie ahead of companies approaching the clinical phase, and how the right partnerships can work wonders.
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A cluster approach to LNP design may facilitate the optimization of LNPs for other administration routes and therapeutics. Lipid nanoparticles can be optimized for the efficient delivery of.
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Lipid nanoparticles (LNPs) are the leading technology for RNA delivery, given the success of the Pfizer/BioNTech and Moderna COVID-19 mRNA (mRNA) vaccines, and small interfering RNA (siRNA) therapies (patisiran). However, optimization of LNP process parameters and compositions for larger RNA payloads such as self-amplifying RNA (saRNA), which can have complex secondary structures, have not.
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Besides CAR expression and mRNA persistence, CAR T cell functionality was analyzed in vitro for 6 days post-transfection. Consistent to CAR expression, CAR T cell efficacy was elongated after LNP-based transfection by up to 3 days indicated by a later peak as well as a slower decrease of cytotoxicity against the CD123-expressing cell line KG-1 compared with EP-transfected CAR T cells (Figure 2 D).
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Many informative reviews about employing LNPs for vaccines and gene therapy [8], [9] have largely focused on how nucleic acid cargo elicits biological changes and enacts therapeutic effects, with less attention to the LNP. In this Review, by contrast, we assess the liposome and the LNP literature with a focus on the various lipid-based building blocks that constitute LNPs in order to explicate.
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The LNP sample for NMR was prepared in 10% D 2 O containing 0.005 wt.% 3-(trimethylsilyl) propionic-2,2,3,3-d4 acid, sodium salt (TSP) for chemical shift calibration. LNP NMR spectra were recorded.
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