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10.1093/nar/gkv762 http://scihub22266oqcxt.onion/10.1093/nar/gkv762 C4652771!4652771!26220182     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nucleic+Acids+Res 2015 ; 43 (16): 7984-8001 Nephropedia Template TP {{tp|p=26220182|t=2015. Identification of siRNA delivery enhancers by a chemical library screen |pdf=|usr=}}{{26220182}} gab.com Text Identification of siRNA delivery enhancers by a chemical library screen JO: Nucleic Acids Res http://www.kidney.de/pget.php?&tw=1&pmid=26220182 #FOAvip Most delivery systems for small interfering RNA therapeutics depend on endocytosis and release from endo-lysosomal compartments. One approach to improve delivery is to identify small molecules enhancing these steps. It is unclear to what extent such enhancers can be universally applied to different delivery systems and cell types. Here, we performed a compound library screen on two well-established siRNA delivery systems, lipid nanoparticles and cholesterol conjugated-siRNAs. We identified fifty-one enhancers improving gene silencing 2?5 fold. Strikingly, most enhancers displayed specificity for one delivery system only. By a combination of quantitative fluorescence and electron microscopy we found that the enhancers substantially differed in their mechanism of action, increasing either endocytic uptake or release of siRNAs from endosomes. Furthermore, they acted either on the delivery system itself or the cell, by modulating the endocytic system via distinct mechanisms. Interestingly, several compounds displayed activity on different cell types. As proof of principle, we showed that one compound enhanced siRNA delivery in primary endothelial cells in vitro and in the endocardium in the mouse heart. This study suggests that a pharmacological approach can improve the delivery of siRNAs in a system-specific fashion, by exploiting distinct mechanisms and acting upon multiple cell types. Twit Text FOAVip Identification of siRNA delivery enhancers by a chemical library screen ????Nucleic Acids Res http://www.kidney.de/pget.php?&tw=1&pmid=26220182 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26220182 #FOAvip English Wikipedia <ref>{{Cite pmid|26220182}}</ref> Identification of siRNA delivery enhancers by a chemical library screen #MMPMID26220182 Gilleron J; Paramasivam P; Zeigerer A; Querbes W; Marsico G; Andree C; Seifert S; Amaya P; Stöter M; Koteliansky V; Waldmann H; Fitzgerald K; Kalaidzidis Y; Akinc A; Maier MA; Manoharan M; Bickle M; Zerial M Nucleic Acids Res 2015[Sep]; 43 (16): 7984-8001 PMID26220182show ga Most delivery systems for small interfering RNA therapeutics depend on endocytosis and release from endo-lysosomal compartments. One approach to improve delivery is to identify small molecules enhancing these steps. It is unclear to what extent such enhancers can be universally applied to different delivery systems and cell types. Here, we performed a compound library screen on two well-established siRNA delivery systems, lipid nanoparticles and cholesterol conjugated-siRNAs. We identified fifty-one enhancers improving gene silencing 2?5 fold. Strikingly, most enhancers displayed specificity for one delivery system only. By a combination of quantitative fluorescence and electron microscopy we found that the enhancers substantially differed in their mechanism of action, increasing either endocytic uptake or release of siRNAs from endosomes. Furthermore, they acted either on the delivery system itself or the cell, by modulating the endocytic system via distinct mechanisms. Interestingly, several compounds displayed activity on different cell types. As proof of principle, we showed that one compound enhanced siRNA delivery in primary endothelial cells in vitro and in the endocardium in the mouse heart. This study suggests that a pharmacological approach can improve the delivery of siRNAs in a system-specific fashion, by exploiting distinct mechanisms and acting upon multiple cell types. äIdentification of siRNA delivery enhancers by a chemical library scree(epmc).pdf DeepDyve Pubget Overpricing