Linked Life Data

18343835

Source:http://linkedlifedata.com/resource/pubmed/id/18343835

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 4
pubmed:dateCreated
2008-3-17
pubmed:abstractText
Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded nucleic acid-analogue antisense agents that enter cells readily and can reduce gene expression by steric blocking of complementary RNA (cRNA) sequences. Here, we tested a panel of PPMO designed to target conserved sequences in the RNA genome segments encoding polymerase subunits of a highly pathogenic mouse-adapted influenza A virus (SC35M; H7N7). Three PPMO, targeting the translation start site region of PB1 or NP mRNA or the 3'-terminal region of NP viral RNA (vRNA), potently inhibited virus replication in MDCK cells. Primer extension assays showed that treatment with any of the effective PPMO led to markedly reduced levels of mRNA, cRNA and vRNA. Initially, the potential toxicity of a range of intranasally administered PPMO doses was evaluated, by measuring their effect on body weight of uninfected mice. Subsequently, a non-toxic dosing regimen was used to investigate the effect of various PPMO on SC35M infection in a mouse model. Mice administered intranasal treatment of PPMO targeting the PB1-AUG region or NP vRNA, at 3 mug per dose, given once 3 h before and once 2 days after intranasal infection with 10xLD(50) of SC35M, showed a 2 log(10) reduction of viral titre in the lungs and 50 % survival for the 16 day duration of the experiment, whereas the NP-AUG-targeted PPMO treatment resulted in 30 % survival of an otherwise lethal infection. These data suggest that PPMO provide a useful reagent to investigate influenza virus molecular biology and may constitute a therapeutic strategy against highly pathogenic influenza viruses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
939-48
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18343835-Administration, Intranasal, pubmed-meshheading:18343835-Animals, pubmed-meshheading:18343835-Anti-Infective Agents, pubmed-meshheading:18343835-Cell Line, pubmed-meshheading:18343835-Dogs, pubmed-meshheading:18343835-Dose-Response Relationship, Drug, pubmed-meshheading:18343835-Drug Administration Schedule, pubmed-meshheading:18343835-Drug Evaluation, Preclinical, pubmed-meshheading:18343835-Gene Targeting, pubmed-meshheading:18343835-Genes, Viral, pubmed-meshheading:18343835-Influenza A Virus, H7N7 Subtype, pubmed-meshheading:18343835-Influenza A virus, pubmed-meshheading:18343835-Mice, pubmed-meshheading:18343835-Mice, Inbred BALB C, pubmed-meshheading:18343835-Morpholines, pubmed-meshheading:18343835-Morpholinos, pubmed-meshheading:18343835-Nucleoproteins, pubmed-meshheading:18343835-Orthomyxoviridae Infections, pubmed-meshheading:18343835-Peptides, pubmed-meshheading:18343835-RNA-Binding Proteins, pubmed-meshheading:18343835-Viral Core Proteins, pubmed-meshheading:18343835-Viral Proteins
pubmed:year
2008
pubmed:articleTitle
Morpholino oligomers targeting the PB1 and NP genes enhance the survival of mice infected with highly pathogenic influenza A H7N7 virus.
pubmed:affiliation
Institute of Virology, Philipps University Marburg, Germany. guelsah.gabriel@path.ox.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't