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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2008-10-27
pubmed:abstractText
MicroRNAs have emerged as important players in tissue-specific mammalian gene regulation and have also been exploited in experimental targeting of gene expression. We have constructed a recombinant adenovirus that contains sequences complementary to the liver-specific microRNA 122 (miR122) in the 3' untranslated region of the E1A gene. In Huh7 cells, which resemble normal hepatocytes in expressing high levels of miR122, this feature resulted in strongly reduced levels of E1A mRNA and protein. This property allowed us to generate a novel recombinant adenovirus that was severely attenuated in cells of hepatic origin but replicated normally in other cells. This strategy may be useful in circumventing liver toxicity associated with the systemic delivery of oncolytic adenoviruses. These data provide the first example of exploiting differential microRNA expression patterns to alter the natural tropism of a DNA virus. In addition, these results suggest that other microRNAs expressed in a tissue- or transformation-specific manner may also be used for the targeting of adenoviral replication and that the same principle may be applied to other viruses that have shown promise as oncolytic or gene delivery platforms.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-10644974, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-11017145, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-11779418, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-11801569, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-11895000, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-12007417, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-12697873, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-12794639, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-12809598, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-14567964, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-14744438, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-14965376, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15122578, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15155160, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15210942, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15286681, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15361871, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15502875, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15607965, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15610730, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15613331, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-15944708, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16299537, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16299539, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16381831, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16446010, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16461460, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16477010, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16557279, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16580264, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-16957370, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17060945, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17179747, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17300834, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17383089, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17504024, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17504025, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17508279, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17613543, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-17878043, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-18026085, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-18560417, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-2146801, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-3943125, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-8832876, http://linkedlifedata.com/resource/pubmed/commentcorrection/18799589-9205053
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1098-5514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11009-15
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Generation of a conditionally replicating adenovirus based on targeted destruction of E1A mRNA by a cell type-specific MicroRNA.
pubmed:affiliation
Department of Virology, Haartman Institute, University of Helsinki, Haartmaninkatu 3 (POB 21), FIN-00014 Helsinki, Finland.
pubmed:publicationType
Journal Article
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