Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles was written by Arteta, Marianna Yanez;Kjellman, Tomas;Bartesaghi, Stefano;Wallin, Simonetta;Wu, Xiaoqiu;Kvist, Alexander J.;Dabkowska, Aleksandra;Szekely, Noemi;Radulescu, Aurel;Bergenholtz, Johan;Lindfors, Lennart. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2018.Synthetic Route of C43H79NO2 The following contents are mentioned in the article:
The development of safe and efficacious gene vectors has limited greatly the potential for therapeutic treatments based on mRNA (mRNA). Lipid nanoparticles (LNPs) formed by an ionizable cationic lipid (here DLin-MC3-DMA), helper lipids (distearoylphosphatidylcholine, DSPC, and cholesterol), and a poly(ethylene glycol) (PEG) lipid have been identified as very promising delivery vectors of short interfering RNA (siRNA) in different clin. phases; however, delivery of high-mol. weight RNA has been proven much more demanding. Herein we elucidate the structure of hEPO modified mRNA-containing LNPs of different sizes and show how structural differences affect transfection of human adipocytes and hepatocytes, two clin. relevant cell types. Employing smallangle scattering, we demonstrate that LNPs have a disordered inverse hexagonal internal structure with a characteristic distance around 6 nm in presence of mRNA, whereas LNPs containing no mRNA do not display this structure. Furthermore, using contrast variation small-angle neutron scattering, we show that one of the lipid components, DSPC, is localized mainly at the surface of mRNAcontaining LNPs. By varying LNP size and surface composition we demonstrate that both size and structure have significant influence on intracellular protein production As an example, in both human adipocytes and hepatocytes, protein expression levels for 130 nm LNPs can differ as much as 50-fold depending on their surface characteristics, likely due to a difference in the ability of LNP fusion with the early endosome membrane.We consider these discoveries to be fundamental and opening up new possibilities for rational design of synthetic nanoscopic vehicles for mRNA delivery. This study involved multiple reactions and reactants, such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7Synthetic Route of C43H79NO2).
(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (cas: 1224606-06-7) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Cyclic esters are called lactones, regardless of whether they are derived from an organic or inorganic acid. One example of an organic lactone is 纬-valerolactone.Synthetic Route of C43H79NO2
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Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics