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10.1039/d0nr06816k http://scihub22266oqcxt.onion/10.1039/d0nr06816k 33241838!ä!33241838 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nanoscale 2020 ; 12 (47): 23959-23966 Nephropedia Template TP {{tp|p=33241838|t=2020. Spontaneous, solvent-free entrapment of siRNA within lipid nanoparticles |pdf=|usr=}}{{33241838}} gab.com Text Spontaneous, solvent-free entrapment of siRNA within lipid nanoparticles JO: Nanoscale http://www.kidney.de/pget.php?&tw=1&pmid=33241838 #FOAvip Lipid nanoparticle (LNP) formulations of nucleic acid are leading vaccine candidates for COVID-19, and enabled the first approved RNAi therapeutic, Onpattro. LNPs are composed of ionizable cationic lipids, phosphatidylcholine, cholesterol, and polyethylene glycol (PEG)-lipids, and are produced using rapid-mixing techniques. These procedures involve dissolution of the lipid components in an organic phase and the nucleic acid in an acidic aqueous buffer (pH 4). These solutions are then combined using a continuous mixing device such as a T-mixer or microfluidic device. In this mixing step, particle formation and nucleic acid entrapment occur. Previous work from our group has shown that, in the absence of nucleic acid, the particles formed at pH 4 are vesicular in structure, a portion of these particles are converted to electron-dense structures in the presence of nucleic acid, and the proportion of electron-dense structures increases with nucleic acid content. What remained unclear from previous work was the mechanism by which vesicles form electron-dense structures. In this study, we use cryogenic transmission electron microscopy and dynamic light scattering to show that efficient siRNA entrapment occurs in the absence of ethanol (contrary to the established paradigm), and suggest that nucleic acid entrapment occurs through inversion of preformed vesicles. We also leverage this phenomenon to show that specialized mixers are not required for siRNA entrapment, and that preformed particles at pH 4 can be used for in vitro transfection. Twit Text FOAVip Spontaneous, solvent-free entrapment of siRNA within lipid nanoparticles ????Nanoscale http://www.kidney.de/pget.php?&tw=1&pmid=33241838 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33241838 #FOAvip English Wikipedia <ref>{{Cite pmid|33241838}}</ref> Spontaneous, solvent-free entrapment of siRNA within lipid nanoparticles #MMPMID33241838 Kulkarni JA; Thomson SB; Zaifman J; Leung J; Wagner PK; Hill A; Tam YYC; Cullis PR; Petkau TL; Leavitt BR Nanoscale 2020[Dec]; 12 (47): 23959-23966 PMID33241838show ga Lipid nanoparticle (LNP) formulations of nucleic acid are leading vaccine candidates for COVID-19, and enabled the first approved RNAi therapeutic, Onpattro. LNPs are composed of ionizable cationic lipids, phosphatidylcholine, cholesterol, and polyethylene glycol (PEG)-lipids, and are produced using rapid-mixing techniques. These procedures involve dissolution of the lipid components in an organic phase and the nucleic acid in an acidic aqueous buffer (pH 4). These solutions are then combined using a continuous mixing device such as a T-mixer or microfluidic device. In this mixing step, particle formation and nucleic acid entrapment occur. Previous work from our group has shown that, in the absence of nucleic acid, the particles formed at pH 4 are vesicular in structure, a portion of these particles are converted to electron-dense structures in the presence of nucleic acid, and the proportion of electron-dense structures increases with nucleic acid content. What remained unclear from previous work was the mechanism by which vesicles form electron-dense structures. In this study, we use cryogenic transmission electron microscopy and dynamic light scattering to show that efficient siRNA entrapment occurs in the absence of ethanol (contrary to the established paradigm), and suggest that nucleic acid entrapment occurs through inversion of preformed vesicles. We also leverage this phenomenon to show that specialized mixers are not required for siRNA entrapment, and that preformed particles at pH 4 can be used for in vitro transfection. |*COVID-19[MESH] |*Lab-On-A-Chip Devices[MESH] |*Lipids/chemistry/pharmacology[MESH] |*Nanoparticles/chemistry/therapeutic use[MESH] |*RNA, Small Interfering/chemistry/pharmacology[MESH] |*SARS-CoV-2[MESH] |Animals[MESH] |Cell Line[MESH] |Hydrogen-Ion Concentration[MESH]Spontaneous, solvent-free entrapment of siRNA within lipid nanoparticl(epmc).pdf DeepDyve Pubget Overpricing