A conditionally replicating adenovirus targeted to tumor cells through activated RAS/P-MAPK-selective mRNA stabilization View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2003-07

AUTHORS

Atique Ahmed, Jill Thompson, Lisa Emiliusen, Stephen Murphy, R Daniel Beauchamp, Kaori Suzuki, Ramon Alemany, Kevin Harrington, Richard G Vile

ABSTRACT

The expression of various proteins associated with rapid responses to inflammation and/or proliferation can be controlled at the level of mRNA stability. Because tumor cells continually recapitulate intracellular programs of proliferation, we have used tumor cell-selective stabilization of mRNA as a means to control therapeutic gene expression. We describe an adenoviral vector that is conditionally replication competent in which expression of the essential adenoviral early region 1A (E1A) gene is regulated by ligation to the 3' untranslated region (UTR) of PTGS2 (also known as COX2), the gene encoding prostaglandin-endoperoxide synthase 2, allowing activated RAS/P-MAPK-specific stabilization of its mRNA. Induction of activated RAS supports replication, whereas matched cells in which activated RAS/P-MAPK is not expressed are very poor substrates for viral replication both in vitro and in vivo. Further tumor-targeting strategies will also be required to prevent viral replication at extratumoral sites where PTGS2 is normally induced. Many different genes contain 3' UTRs that control selective mRNA stability under different physiological, pathological and tumor-associated conditions. Therefore, generating tumor selectivity at the level of mRNA stability is a strategy with broad potential applicability in vector design. More... »

PAGES

771-777

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt835

DOI

http://dx.doi.org/10.1038/nbt835

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015741575

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12794639


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nbt835'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nbt835'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nbt835'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nbt835'


 

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