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10.1016/j.omtn.2017.10.003 http://scihub22266oqcxt.onion/10.1016/j.omtn.2017.10.003 C5675723/?report=reader!5675723!29246303     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Mol+Ther+Nucleic+Acids 2017 ; 9 (ä): 242-50 Nephropedia Template TP {{tp|p=29246303|t=2017. Site-Specific Modification Using the 2?-Methoxyethyl Group Improves the Specificity and Activity of siRNAs |pdf=|usr=}}{{29246303}} gab.com Text Site-Specific Modification Using the 2 -Methoxyethyl Group Improves the Specificity and Activity of siRNAs JO: Mol Ther Nucleic Acids http://www.kidney.de/pget.php?&tw=1&pmid=29246303 #FOAvip Rapid progress has been made toward small interfering RNA (siRNA)-based therapy for human disorders, but rationally optimizing siRNAs for high specificity and potent silencing remains a challenge. In this study, we explored the effect of chemical modification at the cleavage site of siRNAs. We found that modifications at positions 9 and 10 markedly reduced the silencing potency of the unmodified strand of siRNAs but were well tolerated by the modified strand. Intriguingly, addition of the 2?-methoxyethyl (MOE) group at the cleavage site improved both the specificity and silencing activity of siRNAs by facilitating the oriented RNA-induced silencing complex (RISC) loading of the modified strand. Furthermore, we combined MOE modifications at positions 9 and 10 of one strand together with 2?-O-methylation (OMe) at position 14 of the other strand and found a synergistic effect that improved the specificity of siRNAs. The surprisingly beneficial effect of the combined modification was validated using siRNA-targeting endogenous gene intercellular adhesion molecule 1 (ICAM1). We found that the combined modifications eliminated its off-target effects. In conclusion, we established effective strategies to optimize siRNAs using site-specific MOE modifications. The findings may allow the creation of superior siRNAs for therapy in terms of activity and specificity. Twit Text FOAVip Site-Specific Modification Using the 2 -Methoxyethyl Group Improves the Specificity and Activity of siRNAs ????Mol Ther Nucleic Acids http://www.kidney.de/pget.php?&tw=1&pmid=29246303 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29246303 #FOAvip English Wikipedia <ref>{{Cite pmid|29246303}}</ref> Site-Specific Modification Using the 2?-Methoxyethyl Group Improves the Specificity and Activity of siRNAs #MMPMID29246303 Song X; Wang X; Ma Y; Liang Z; Yang Z; Cao H Mol Ther Nucleic Acids 2017[Dec]; 9 (ä): 242-50 PMID29246303show ga Rapid progress has been made toward small interfering RNA (siRNA)-based therapy for human disorders, but rationally optimizing siRNAs for high specificity and potent silencing remains a challenge. In this study, we explored the effect of chemical modification at the cleavage site of siRNAs. We found that modifications at positions 9 and 10 markedly reduced the silencing potency of the unmodified strand of siRNAs but were well tolerated by the modified strand. Intriguingly, addition of the 2?-methoxyethyl (MOE) group at the cleavage site improved both the specificity and silencing activity of siRNAs by facilitating the oriented RNA-induced silencing complex (RISC) loading of the modified strand. Furthermore, we combined MOE modifications at positions 9 and 10 of one strand together with 2?-O-methylation (OMe) at position 14 of the other strand and found a synergistic effect that improved the specificity of siRNAs. The surprisingly beneficial effect of the combined modification was validated using siRNA-targeting endogenous gene intercellular adhesion molecule 1 (ICAM1). We found that the combined modifications eliminated its off-target effects. In conclusion, we established effective strategies to optimize siRNAs using site-specific MOE modifications. The findings may allow the creation of superior siRNAs for therapy in terms of activity and specificity. äSite-Specific Modification Using the 2?-Methoxyethyl Group Improves th(epmc).pdf DeepDyve Pubget Overpricing