Genomes and Genes
Affiliation: University of Pennsylvania
- Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activationBart R Anderson
Department of Medicine, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA
Nucleic Acids Res 38:5884-92. 2010..These results indicate that the enhanced translation of mRNAs containing pseudouridine, compared to those containing uridine, is mediated by decreased activation of PKR...
- Nucleoside modifications in RNA limit activation of 2'-5'-oligoadenylate synthetase and increase resistance to cleavage by RNase LBart R Anderson
Department of Medicine, 3610 Hamilton Walk, 522B Johnson Pavilion, University of Pennsylvania, Philadelphia, PA 19104, USA
Nucleic Acids Res 39:9329-38. 2011....
- Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietinKatalin Kariko
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Mol Ther 20:948-53. 2012..These results demonstrate that HPLC-purified, pseudouridine-containing mRNAs encoding therapeutic proteins have great potential for clinical applications...
- Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stabilityKatalin Kariko
Department of Neurosurgery, University of Pennsylvania, Room 371 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, Pennsylvania 19104 6087, USA
Mol Ther 16:1833-40. 2008..Improved properties conferred by pseudouridine make such mRNA a promising tool for both gene replacement and vaccination...
- Naturally occurring nucleoside modifications suppress the immunostimulatory activity of RNA: implication for therapeutic RNA developmentKatalin Kariko
Department of Neurosurgery, University of Pennsylvania, Rm 371 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104, USA
Curr Opin Drug Discov Devel 10:523-32. 2007..RNAs containing modified nucleosides, and thus lacking immune-activating properties, have potential importance in clinical applications...
- Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNAKatalin Kariko
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
Immunity 23:165-75. 2005..The innate immune system may therefore detect RNA lacking nucleoside modification as a means of selectively responding to bacteria or necrotic tissue...
- Inhibition of toll-like receptor and cytokine signaling--a unifying theme in ischemic toleranceKatalin Kariko
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
J Cereb Blood Flow Metab 24:1288-304. 2004..This novel interpretation of the molecular mechanism of ischemic tolerance highlights new avenues for future investigation into the prevention and treatment of stroke and related diseases...
- Phosphate-enhanced transfection of cationic lipid-complexed mRNA and plasmid DNAK Kariko
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Biochim Biophys Acta 1369:320-34. 1998..These findings delineate specific conditions which dramatically enhance transfection efficiency for both DNA and mRNA, and provide an effective procedure for gene transfection studies...
- In vivo protein expression from mRNA delivered into adult rat brainK Kariko
Department of Neurosurgery, University of Pennsylvania School of Medicine, Room 371 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104 6070, USA
J Neurosci Methods 105:77-86. 2001....
- mRNA is an endogenous ligand for Toll-like receptor 3Katalin Kariko
Division of Neurosurgery and Infectious Diseases, University of Pennsylvania, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
J Biol Chem 279:12542-50. 2004..This finding has potential physiologic relevance because RNA escaping from damaged tissue or contained within endocytosed cells could serve as an endogenous ligand for TLR3 that induces or otherwise modulates immune responses...
- Platelet factor 4 binds to low-density lipoprotein receptors and disrupts the endocytic machinery, resulting in retention of low-density lipoprotein on the cell surfaceBruce S Sachais
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA
Blood 99:3613-22. 2002..Retention of LDL on cell surfaces may facilitate proatherogenic modifications and support an expanded role for platelets in the pathogenesis of atherosclerosis...
- Cutting edge: innate immune system discriminates between RNA containing bacterial versus eukaryotic structural features that prime for high-level IL-12 secretion by dendritic cellsGary K Koski
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 172:3989-93. 2004..RNA structured to emulate bacterial patterns constitutes a novel vaccine strategy to engender polarized Th1-type immune responses...
- Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through toll-like receptor 3Katalin Kariko
Division of Neurosurgery and Infectious Diseases, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 172:6545-9. 2004..Although siRNA and shRNA knockdown of genes represents a new and powerful tool, it is not without nonspecific effects, which we demonstrate are mediated in part by signaling through TLR3...
- Nucleofection induces transient eIF2α phosphorylation by GCN2 and PERKB R Anderson
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104 6073, USA
Gene Ther 20:136-42. 2013..Strategies to circumvent eIF2α phosphorylation and other downstream effects of activating GCN2 and PERK will facilitate further advancement of nucleic acid-based therapies...
- HIV gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune responseD Weissman
Division of Infectious Diseases and Neurosurgery, University of Pennsylvania, Philadelphia, PA 19096, USA
J Immunol 165:4710-7. 2000....
- gp340 expressed on human genital epithelia binds HIV-1 envelope protein and facilitates viral transmissionEarl Stoddard
Department of Medicine, Division of Infectious Diseases, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 179:3126-32. 2007..Understanding this step in the initiation of infection will allow for the development of tools and methods for blocking HIV transmission...
- Short interfering RNA-mediated inhibition of herpes simplex virus type 1 gene expression and function during infection of human keratinocytesPrakash K Bhuyan
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
J Virol 78:10276-81. 2004..This work establishes RNAi as a genetic tool for the study of HSV and provides a foundation for development of RNAi as a novel antiviral therapy...
- Erythropoietin-encoding mRNA for treatment of anemiaKatalin Kariko; Fiscal Year: 2007....