Linked Life Data

17390017

Source:http://linkedlifedata.com/resource/pubmed/id/17390017

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-3-28
pubmed:abstractText
Low transduction efficiencies of viral and non-viral vectors still remain a major limitation in suicide gene therapy. The HSV-1 tegument protein VP22 can spread from cells where it is produced to surrounding recipient cells, thus making it a promising tool for compensation of inadequate gene transfer efficiencies. In our previous study, we focused on the optimization of the cytosine deaminase (CD) suicide gene system for the treatment of hepatocellular carcinoma. The fusion of yeast cytosine deaminase (YCD) to yeast uracil-phosphoribosyltransferase designated SuperCD was shown to be catalytically superior to the YCD gene in our previous study. The aim of our study was to investigate whether fusion of the bifunctional SuperCD suicide gene to VP22 could further potentiate suicide gene therapy efficiency. C- and N-terminal fusions of SuperCD linked in-frame with VP22 were created and cloned into recombinant adenoviral vectors. Under incubation with the prodrug 5-fluorocytosine (5-FC) a strong enhancement in suicide gene induced target cell cytotoxicity was observed whereby the C-terminal fusion of VP22 to SuperCD (VP22-SuperCD) caused the most tremendous decrease in IC50 compared to both Ad-SuperCD transduced and uninfected hepatoma control cells. Optimization of the bystander effect mediated by the intercellular transport of VP22-fusion proteins was demonstrated by cytotoxicity assays performed with a mixture of adenoviral transduced cells and naïve uninfected cells. Immunofluorescence analysis of adenoviral transduced COS-1 cells coplated with naïve HeLa cells further confirmed the unique property of VP22 for intercellular trafficking.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1153-61
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Fusion of HSV-1 VP22 to a bifunctional chimeric SuperCD suicide gene compensates for low suicide gene transduction efficiencies.
pubmed:affiliation
Department of Internal Medicine I, University Clinic Tübingen, Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't