Linked Life Data

11127582

Source:http://linkedlifedata.com/resource/pubmed/id/11127582

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2000-12-20
pubmed:abstractText
Adenoviral vector systems for gene therapy can be much improved by targeting vectors to specific cell types. This requires both the complete ablation of native adenovirus tropism and the introduction of a novel binding affinity in the viral capsid. We reasoned that these requirements could be fulfilled by deleting the entire knob domain of the adenovirus fiber protein and replacing it with two distinct moieties that provide a trimerization function for the knobless fiber and specific binding to the target cell, respectively. To test this concept, we constructed adenoviral vectors carrying knobless fibers comprising the alpha-helix trimerization domain from MoMuLV envelope glycoprotein. Two mimic targeting ligands, a Myc-epitope and a 6His-tag, were attached via a flexible linker peptide. The targeted knobless fiber molecules were properly expressed and imported into the nucleus of adenovirus packaging cells, where they were incorporated as functional trimers into the adenovirus capsid. Both ligands were exposed on the surface of the virion and were available for specific binding to their target molecules. Moreover, the knobless fibers mediated gene delivery into cells displaying receptors for the coupled ligand. Hence, these knobless fibers are prototype substrates for versatile addition of targeting ligands to generate truly targeted adenoviruses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1940-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Recombinant adenovirus vectors with knobless fibers for targeted gene transfer.
pubmed:affiliation
Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't