Linked Life Data

19537946

Source:http://linkedlifedata.com/resource/pubmed/id/19537946

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-10-23
pubmed:abstractText
Tumor targeting on systemic adenovirus administration is key to improve the prospects of adenovirus-mediated gene therapy and virus therapy of cancer. Despite many genetic and ligand conjugation approaches this objective remains elusive. Ablation of human adenovirus type 5 (Ad5) binding to its natural receptors in airway epithelial cells, that is, the coxsackievirus and adenovirus receptor (CAR) and integrins, does not impact on the preeminent liver tropism of adenovirus in the bloodstream. This is explained by a distinct entry pathway mediated by blood factors and heparan sulfates. Mutation of the KKTK heparin sulfate-binding domain of the fiber shaft to GATK results in liver transduction detargeting, but it is not compatible with otherwise useful HI-loop tumor-targeting ligand insertions such as the insertion of Arg-Gly-Asp (RGD). To circumvent this problem we have mutated the KKTK domain to RGDK, and analyzed the liver-detargeting and tumor-targeting transduction properties of this replacement mutant. Similar to RGD at the HI-loop, RGD at this new shaft location efficiently enhances the infectivity of adenovirus and improves the tumor-to-liver transduction ratio in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1557-7422
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1214-21
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Replacement of adenovirus type 5 fiber shaft heparan sulfate proteoglycan-binding domain with RGD for improved tumor infectivity and targeting.
pubmed:affiliation
Translational Research Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)-Institut Català d'Oncologia, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't