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10.1016/j.ymthe.2020.11.011 http://scihub22266oqcxt.onion/10.1016/j.ymthe.2020.11.011 33352107!7935664!33352107     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Mol+Ther 2021 ; 29 (3): 1174-1185 Nephropedia Template TP {{tp|p=33352107|t=2021. Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA |pdf=|usr=}}{{33352107}} gab.com Text Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA JO: Mol Ther http://www.kidney.de/pget.php?&tw=1&pmid=33352107 #FOAvip Self-amplifying RNA (saRNA) is a cutting-edge platform for both nucleic acid vaccines and therapeutics. saRNA is self-adjuvanting, as it activates types I and III interferon (IFN), which enhances the immunogenicity of RNA vaccines but can also lead to inhibition of translation. In this study, we screened a library of saRNA constructs with cis-encoded innate inhibiting proteins (IIPs) and determined the effect on protein expression and immunogenicity. We observed that the PIV-5 V and Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a proteins enhance protein expression 100- to 500-fold in vitro in IFN-competent HeLa and MRC5 cells. We found that the MERS-CoV ORF4a protein partially abates dose nonlinearity in vivo, and that ruxolitinib, a potent Janus kinase (JAK)/signal transducer and activator of transcription (STAT) inhibitor, but not the IIPs, enhances protein expression of saRNA in vivo. Both the PIV-5 V and MERS-CoV ORF4a proteins were found to enhance the percentage of resident cells in human skin explants expressing saRNA and completely rescued dose nonlinearity of saRNA. Finally, we observed that the MERS-CoV ORF4a increased the rabies virus (RABV)-specific immunoglobulin G (IgG) titer and neutralization half-maximal inhibitory concentration (IC(50)) by approximately 10-fold in rabbits, but not in mice or rats. These experiments provide a proof of concept that IIPs can be directly encoded into saRNA vectors and effectively abate the nonlinear dose dependency and enhance immunogenicity. Twit Text FOAVip Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA ????Mol Ther http://www.kidney.de/pget.php?&tw=1&pmid=33352107 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33352107 #FOAvip English Wikipedia <ref>{{Cite pmid|33352107}}</ref> Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA #MMPMID33352107 Blakney AK; McKay PF; Bouton CR; Hu K; Samnuan K; Shattock RJ Mol Ther 2021[Mar]; 29 (3): 1174-1185 PMID33352107show ga Self-amplifying RNA (saRNA) is a cutting-edge platform for both nucleic acid vaccines and therapeutics. saRNA is self-adjuvanting, as it activates types I and III interferon (IFN), which enhances the immunogenicity of RNA vaccines but can also lead to inhibition of translation. In this study, we screened a library of saRNA constructs with cis-encoded innate inhibiting proteins (IIPs) and determined the effect on protein expression and immunogenicity. We observed that the PIV-5 V and Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a proteins enhance protein expression 100- to 500-fold in vitro in IFN-competent HeLa and MRC5 cells. We found that the MERS-CoV ORF4a protein partially abates dose nonlinearity in vivo, and that ruxolitinib, a potent Janus kinase (JAK)/signal transducer and activator of transcription (STAT) inhibitor, but not the IIPs, enhances protein expression of saRNA in vivo. Both the PIV-5 V and MERS-CoV ORF4a proteins were found to enhance the percentage of resident cells in human skin explants expressing saRNA and completely rescued dose nonlinearity of saRNA. Finally, we observed that the MERS-CoV ORF4a increased the rabies virus (RABV)-specific immunoglobulin G (IgG) titer and neutralization half-maximal inhibitory concentration (IC(50)) by approximately 10-fold in rabbits, but not in mice or rats. These experiments provide a proof of concept that IIPs can be directly encoded into saRNA vectors and effectively abate the nonlinear dose dependency and enhance immunogenicity. |*Immunogenicity, Vaccine[MESH] |Animals[MESH] |Cell Line[MESH] |Encephalitis Virus, Venezuelan Equine/drug effects/immunology/pathogenicity[MESH] |Fibroblasts[MESH] |Gene Expression Regulation[MESH] |HeLa Cells[MESH] |Host-Pathogen Interactions/genetics/immunology[MESH] |Humans[MESH] |Immunity, Innate/*drug effects[MESH] |Immunoglobulin G/biosynthesis[MESH] |Interferon Regulatory Factor-3/genetics/immunology[MESH] |Janus Kinases/antagonists & inhibitors/genetics/immunology[MESH] |Mice[MESH] |Middle East Respiratory Syndrome Coronavirus/drug effects/immunology/pathogenicity[MESH] |NF-kappa B/genetics/immunology[MESH] |Nitriles[MESH] |Parainfluenza Virus 5/drug effects/immunology/pathogenicity[MESH] |Protein Biosynthesis/*drug effects[MESH] |Pyrazoles/pharmacology[MESH] |Pyrimidines[MESH] |Rabbits[MESH] |Rabies virus/drug effects/immunology/pathogenicity[MESH] |Rats[MESH] |STAT Transcription Factors/antagonists & inhibitors/genetics/immunology[MESH] |Signal Transduction[MESH] |Vaccines, Synthetic/biosynthesis/*pharmacology[MESH] |Viral Envelope Proteins/*administration & dosage/genetics/immunology[MESH]Innate Inhibiting Proteins Enhance Expression and Immunogenicity of S(epmc).pdf DeepDyve Pubget Overpricing