Linked Life Data

18026085

Source:http://linkedlifedata.com/resource/pubmed/id/18026085

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2007-12-10
pubmed:abstractText
We have shown previously that transgene expression can be suppressed in hematopoietic cells using vectors that are responsive to microRNA (miRNA) regulation. Here we investigate the potential of this approach for more sophisticated control of transgene expression. Analysis of the relationship between miRNA expression levels and target mRNA suppression suggested that suppression depends on a threshold miRNA concentration. Using this information, we generated vectors that rapidly adjust transgene expression in response to changes in miRNA expression. These vectors sharply segregated transgene expression between closely related states of therapeutically relevant cells, including dendritic cells, hematopoietic and embryonic stem cells, and their progeny, allowing positive/negative selection according to the cells' differentiation state. Moreover, two miRNA target sites were combined to restrict transgene expression to a specific cell type in the liver. Notably, the vectors did not detectably perturb endogenous miRNA expression or regulation of natural targets. The properties of miRNA-regulated vectors should allow for safer and more effective therapeutic applications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1546-1696
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1457-67
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state.
pubmed:affiliation
San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, via Olgettina, 58, 20132 Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't