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Thanks to the LNP-mRNA vaccine that came to the fore during the COVID-19 pandemic, lipid nanoparticles (LNP) are undoubtedly the most advanced and widely studied non-viral vectors at present. Typically, LNP is composed of 4 components: ionizable cationic lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids. Each component.
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While LNP is a promising drug delivery system, major accumulation of LNP in the liver by ApoE-LDL interaction has hindered the successful development of mRNA/LNPs to treat extra-hepatic diseases. To expand the use of LNPs to target extra-hepatic organs, it is necessary to develop strategies to effectively target specific organs and tissues in.
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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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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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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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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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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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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).