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About:
Drug Delivery–mediated Control of RNA Immunostimulation
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covidontheweb.inria.fr
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Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Drug Delivery–mediated Control of RNA Immunostimulation
Creator
Novobrantseva, Tatiana
Chen, Jianzhu
Chen, Steve C-Y
Goldberg, Michael
Kim, Phillip
Langer, Robert
Lu, James
Sherman, Jennifer
Shulga-Morskaya, Svetlana
Sprague, Andrew
Anderson, Daniel
De Fougerolles, Antonin
Nguyen, David
Source
Elsevier; Medline; PMC
abstract
RNA interference (RNAi) has generated significant interest as a strategy to suppress viral infection, but in some cases antiviral activity of unmodified short-interfering RNA (siRNA) has been attributed to activation of innate immune responses. We hypothesized that immunostimulation by unmodified siRNA could mediate both RNAi as well as innate immune stimulation depending on the mode of drug delivery. We investigated the potential of immunostimulatory RNAs (isRNAs) to suppress influenza A virus in vivo in the mouse lung. Lipidoid 98N12-5(1) formulated with unmodified siRNA targeting the influenza nucleoprotein gene exhibited antiviral activity. Formulations were optimized to increase antiviral activity, but the antiviral activity of lipidoid-delivered siRNA did not depend on sequence homology to the influenza genome as siRNA directed against unrelated targets also suppressed influenza replication in vivo. This activity was primarily attributed to enhancement of innate immune stimulation by lipidoid-mediated delivery, which indicates increased toll-like receptor (TLR) activation by siRNA. Certain chemical modifications to the siRNA backbone, which block TLR7/8 activation but retain in vitro RNAi activity, prevented siRNA-mediated antiviral activity despite enhanced lipidoid-mediated delivery. Here, we demonstrate that innate immune activation caused by unmodified siRNA can have therapeutically relevant effects, and that these non-RNAi effects can be controlled through chemical modifications and drug delivery.
has issue date
2009-09-01
(
xsd:dateTime
)
bibo:doi
10.1038/mt.2009.147
bibo:pmid
19584813
has license
hybrid-oa
sha1sum (hex)
d06e52597d4ab4906bad8ca520341ff7d6edf885
schema:url
https://doi.org/10.1038/mt.2009.147
resource representing a document's title
Drug Delivery–mediated Control of RNA Immunostimulation
has PubMed Central identifier
PMC2835254
has PubMed identifier
19584813
schema:publication
Molecular Therapy
resource representing a document's body
covid:d06e52597d4ab4906bad8ca520341ff7d6edf885#body_text
is
schema:about
of
named entity 'CONTROL'
named entity 'DELIVERY'
named entity 'MEDIATED'
named entity 'RNA'
named entity 'DRUG DELIVERY'
named entity 'IMMUNOSTIMULATION'
named entity 'mmol/l'
named entity 'housekeeping gene'
named entity 'delivery systems'
named entity 'antiviral activity'
named entity 'anti-influenza'
named entity 'TLR3'
named entity 'RNAi'
named entity 'mice'
named entity 'uridine'
named entity 'siRNA'
named entity 'flu'
named entity 'IFN'
named entity 'branched DNA assay'
named entity 'siRNA'
named entity 'immunostimulation'
named entity 'RNAi'
named entity 'TLR8'
named entity 'bDNA'
named entity 'homogenized'
named entity 'RNAi'
named entity 'mice'
named entity 'IFN'
named entity 'influenza infection'
named entity 'prophylactic'
named entity 'genome'
named entity 'siRNA'
named entity 'mRNA'
named entity 'base sequence'
named entity 'gene'
named entity 'RNA interference'
named entity 'antiviral activity'
named entity 'late endosome'
named entity 'PBS'
named entity 'Fluorescence'
named entity 'RNAi'
named entity 'cholesterol'
named entity 'cleavage site'
named entity 'Indianapolis'
named entity 'dsRNA'
named entity 'Madin-Darby canine kidney cells'
named entity 'nanoparticles'
named entity 'hepatitis'
named entity 'liver'
named entity 'siRNA'
named entity 'siNP'
named entity 'liquid nitrogen'
named entity 'siRNA'
named entity 'streptomycin'
named entity 'serum'
named entity 'RNA'
named entity 'siRNAs'
named entity 'HEPES'
named entity 'mice'
named entity 'virus'
named entity 'nmol/l'
named entity 'mRNA'
named entity 'xylazine'
named entity 'RNAi'
named entity 'transfection'
named entity 'siRNAs'
named entity 'antiviral activity'
named entity 'TLR'
named entity 'RNA'
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