scholarly journals Cholesterol Modification of p40-Specific Small Interfering RNA Enables Therapeutic Targeting of Dendritic Cells

2015 ◽  
Vol 195 (5) ◽  
pp. 2216-2223 ◽  
Author(s):  
Jürgen Brück ◽  
Steve Pascolo ◽  
Kerstin Fuchs ◽  
Christina Kellerer ◽  
Ivana Glocova ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Small Interfering Rna ◽  
Therapeutic Targeting ◽  
Cholesterol Modification ◽  
Interfering Rna

scholarly journals Culture medium used during small interfering RNA (siRNA) transfection determines the maturation status of dendritic cells

2020 ◽  
Vol 479 ◽  
pp. 112748
Author(s):  
Mieke F. van Essen ◽  
Nicole Schlagwein ◽  
Daniëlle J. van Gijlswijk-Janssen ◽  
Jacqueline D.H. Anholts ◽  
Michael Eikmans ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Small Interfering Rna ◽  
Culture Medium ◽  
Sirna Transfection ◽  
Interfering Rna

scholarly journals CD83 Knockdown in Monocyte-Derived Dendritic Cells by Small Interfering RNA Leads to a Diminished T Cell Stimulation

2007 ◽  
Vol 178 (9) ◽  
pp. 5454-5464 ◽  
Author(s):  
Alexander T. Prechtel ◽  
Nadine M. Turza ◽  
Alexandros A. Theodoridis ◽  
Alexander Steinkasserer
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Small Interfering Rna ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Interfering Rna

scholarly journals Efficient Inhibition of Avian and Seasonal Influenza A Viruses by a Virus-Specific Dicer-Substrate Small Interfering RNA Swarm in Human Monocyte-Derived Macrophages and Dendritic Cells

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Miao Jiang ◽  
Pamela Österlund ◽  
Veera Westenius ◽  
Deyin Guo ◽  
Minna M. Poranen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Small Interfering Rna ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Primary Monocyte ◽  
Prevention And Treatment ◽  
Interfering Rna

ABSTRACTInfluenza A viruses (IAVs) are viral pathogens that cause epidemics and occasional pandemics of significant mortality. The generation of efficacious vaccines and antiviral drugs remains a challenge due to the rapid appearance of new influenza virus types and antigenic variants. Consequently, novel strategies for the prevention and treatment of IAV infections are needed, given the limitations of the presently available antivirals. Here, we used enzymatically produced IAV-specific double-stranded RNA (dsRNA) molecules andGiardia intestinalisDicer for the generation of a swarm of small interfering RNA (siRNA) molecules. The siRNAs target multiple conserved genomic regions of the IAVs. In mammalian cells, the produced 25- to 27-nucleotide-long siRNA molecules are processed by endogenous Dicer into 21-nucleotide siRNAs and are thus designated Dicer-substrate siRNAs (DsiRNAs). We evaluated the efficacy of the above DsiRNA swarm at preventing IAV infections in human primary monocyte-derived macrophages and dendritic cells. The replication of different IAV strains, including avian influenza H5N1 and H7N9 viruses, was significantly inhibited by pretransfection of the cells with the IAV-specific DsiRNA swarm. Up to 7 orders of magnitude inhibition of viral RNA expression was observed, which led to a dramatic inhibition of IAV protein synthesis and virus production. The IAV-specific DsiRNA swarm inhibited virus replication directly through the RNA interference pathway although a weak induction of innate interferon responses was detected. Our results provide direct evidence for the feasibility of the siRNA strategy and the potency of DsiRNA swarms in the prevention and treatment of influenza, including the highly pathogenic avian influenza viruses.IMPORTANCEIn spite of the enormous amount of research, influenza virus is still one of the major challenges for medical virology due to its capacity to generate new variants, which potentially lead to severe epidemics and pandemics. We demonstrated here that a swarm of small interfering RNA (siRNA) molecules, including more than 100 different antiviral RNA molecules targeting the most conserved regions of the influenza A virus genome, could efficiently inhibit the replication of all tested avian and seasonal influenza A variants in human primary monocyte-derived macrophages and dendritic cells. The wide antiviral spectrum makes the virus-specific siRNA swarm a potentially efficient treatment modality against both avian and seasonal influenza viruses.

scholarly journals Targeted Delivery of Small Interfering RNA to Human Dendritic Cells To Suppress Dengue Virus Infection and Associated Proinflammatory Cytokine Production

2009 ◽  
Vol 84 (5) ◽  
pp. 2490-2501 ◽  
Author(s):  
Sandesh Subramanya ◽  
Sang-Soo Kim ◽  
Sojan Abraham ◽  
Jiahong Yao ◽  
Mukesh Kumar ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dengue Virus ◽  
Virus Replication ◽  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Envelope Gene ◽  
Hematopoietic Stem ◽  
Tnf Α ◽  
Interfering Rna

ABSTRACT Dengue is a common arthropod-borne flaviviral infection in the tropics, for which there is no vaccine or specific antiviral drug. The infection is often associated with serious complications such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), in which both viral and host factors have been implicated. RNA interference (RNAi) is a potent antiviral strategy and a potential therapeutic option for dengue if a feasible strategy can be developed for delivery of small interfering RNA (siRNA) to dendritic cells (DCs) and macrophages, the major in vivo targets of the virus and also the source of proinflammatory cytokines. Here we show that a dendritic cell-targeting 12-mer peptide (DC3) fused to nona-d-arginine (9dR) residues (DC3-9dR) delivers siRNA and knocks down endogenous gene expression in heterogenous DC subsets, (monocyte-derived DCs [MDDCs], CD34+ hematopoietic stem cell [HSC])-derived Langerhans DCs, and peripheral blood DCs). Moreover, DC3-9dR-mediated delivery of siRNA targeting a highly conserved sequence in the dengue virus envelope gene (siFvED) effectively suppressed dengue virus replication in MDDCs and macrophages. In addition, DC-specific delivery of siRNA targeting the acute-phase cytokine tumor necrosis factor alpha (TNF-α), which plays a major role in dengue pathogenesis, either alone or in combination with an antiviral siRNA, significantly reduced virus-induced production of the cytokine in MDDCs. Finally to validate the strategy in vivo, we tested the ability of the peptide to target human DCs in the NOD/SCID/IL-2Rγ−/− mouse model engrafted with human CD34+ hematopoietic stem cells (HuHSC mice). Treatment of mice by intravenous (i.v.) injection of DC3-9dR-complexed siRNA targeting TNF-α effectively suppressed poly(I:C)-induced TNF-α production by DCs. Thus, DC3-9dR can deliver siRNA to DCs both in vitro and in vivo, and this delivery approach holds promise as a therapeutic strategy to simultaneously suppress virus replication and curb virus-induced detrimental host immune responses in dengue infection.

scholarly journals Immune Modulation by Silencing IL-12 Production in Dendritic Cells Using Small Interfering RNA

2003 ◽  
Vol 171 (2) ◽  
pp. 691-696 ◽  
Author(s):  
Jonathan A. Hill ◽  
Thomas E. Ichim ◽  
Kornel P. Kusznieruk ◽  
Mu Li ◽  
Xuyan Huang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Small Interfering Rna ◽  
Immune Modulation ◽  
Interfering Rna

scholarly journals Small Interfering RNA-Mediated Knockdown of Notch Ligands in Primary CD4+ T Cells and Dendritic Cells Enhances Cytokine Production

2006 ◽  
Vol 177 (2) ◽  
pp. 885-895 ◽  
Author(s):  
Yvette Stallwood ◽  
Emmanuel Briend ◽  
Katrina M. Ray ◽  
George A. Ward ◽  
Beverley J. Smith ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Small Interfering Rna ◽  
Cytokine Production ◽  
Interfering Rna ◽  
Notch Ligands

Small interfering RNA (siRNA) delivery into monocyte-derived dendritic cells by electroporation

2006 ◽  
Vol 311 (1-2) ◽  
pp. 139-152 ◽  
Author(s):  
Alexander T. Prechtel ◽  
Nadine M. Turza ◽  
Alexandros A. Theodoridis ◽  
Mirko Kummer ◽  
Alexander Steinkasserer
Keyword(s):  
Dendritic Cells ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Interfering Rna

Small interfering RNA (siRNA) delivery into murine bone marrow-derived dendritic cells by electroporation

2008 ◽  
Vol 337 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Jonathan Jantsch ◽  
Nadine Turza ◽  
Melanie Volke ◽  
Kai-Uwe Eckardt ◽  
Michael Hensel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Murine Bone Marrow ◽  
Interfering Rna
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