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10.1038/s41467-018-04048-4 http://scihub22266oqcxt.onion/10.1038/s41467-018-04048-4 C5920046!5920046!29700298     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Commun 2018 ; 9 (ä): ä Nephropedia Template TP {{tp|p=29700298|t=2018. RNA-guided transcriptional silencing in vivo with S aureus CRISPR-Cas9 repressors |pdf=|usr=}}{{29700298}} gab.com Text RNA-guided transcriptional silencing in vivo with S aureus CRISPR-Cas9 repressors JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=29700298 #FOAvip CRISPR-Cas9 transcriptional repressors have emerged as robust tools for disrupting gene regulation in vitro but have not yet been adapted for systemic delivery in adult animal models. Here we describe a Staphylococcus aureus Cas9-based repressor (dSaCas9KRAB) compatible with adeno-associated viral (AAV) delivery. To evaluate dSaCas9KRAB efficacy for gene silencing in vivo, we silenced transcription of Pcsk9, a regulator of cholesterol levels, in the liver of adult mice. Systemic administration of a dual-vector AAV8 system expressing dSaCas9KRAB and a Pcsk9-targeting guide RNA (gRNA) results in significant reductions of serum Pcsk9 and cholesterol levels. Despite a moderate host response to dSaCas9KRAB expression, Pcsk9 repression is maintained for 24 weeks after a single treatment, demonstrating the potential for long-term gene silencing in post-mitotic tissues with dSaCas9KRAB. In vivo programmable gene silencing enables studies that link gene regulation to complex phenotypes and expands the CRISPR-Cas9 perturbation toolbox for basic research and gene therapy applications. Twit Text FOAVip RNA-guided transcriptional silencing in vivo with S aureus CRISPR-Cas9 repressors ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=29700298 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29700298 #FOAvip English Wikipedia <ref>{{Cite pmid|29700298}}</ref> RNA-guided transcriptional silencing in vivo with S aureus CRISPR-Cas9 repressors #MMPMID29700298 Thakore PI; Kwon JB; Nelson CE; Rouse DC; Gemberling MP; Oliver ML; Gersbach CA Nat Commun 2018[]; 9 (ä): ä PMID29700298show ga CRISPR-Cas9 transcriptional repressors have emerged as robust tools for disrupting gene regulation in vitro but have not yet been adapted for systemic delivery in adult animal models. Here we describe a Staphylococcus aureus Cas9-based repressor (dSaCas9KRAB) compatible with adeno-associated viral (AAV) delivery. To evaluate dSaCas9KRAB efficacy for gene silencing in vivo, we silenced transcription of Pcsk9, a regulator of cholesterol levels, in the liver of adult mice. Systemic administration of a dual-vector AAV8 system expressing dSaCas9KRAB and a Pcsk9-targeting guide RNA (gRNA) results in significant reductions of serum Pcsk9 and cholesterol levels. Despite a moderate host response to dSaCas9KRAB expression, Pcsk9 repression is maintained for 24 weeks after a single treatment, demonstrating the potential for long-term gene silencing in post-mitotic tissues with dSaCas9KRAB. In vivo programmable gene silencing enables studies that link gene regulation to complex phenotypes and expands the CRISPR-Cas9 perturbation toolbox for basic research and gene therapy applications. äRNA-guided transcriptional silencing in vivo with S aureus CRISPR-Cas(epmc).pdf DeepDyve Pubget Overpricing