Linked Life Data

20807602

Source:http://linkedlifedata.com/resource/pubmed/id/20807602

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-9-2
pubmed:abstractText
Gene therapy and molecular-genetic imaging have faced a major problem: the lack of an efficient systemic gene delivery vector. Unquestionably, eukaryotic viruses have been the vectors of choice for gene delivery to mammalian cells; however, they have had limited success in systemic gene therapy. This is mainly due to undesired uptake by the liver and reticuloendothelial system, broad tropism for mammalian cells causing toxicity, and their immunogenicity. On the other hand, prokaryotic viruses such as bacteriophage (phage) have no tropism for mammalian cells, but can be engineered to deliver genes to these cells. However, phage-based vectors have inherently been considered poor vectors for mammalian cells. We have reported a new generation of vascular-targeted systemic hybrid prokaryotic-eukaryotic vectors as chimeras between an adeno-associated virus (AAV) and targeted bacteriophage (termed AAV/phage; AAVP). In this hybrid vector, the targeted bacteriophage serves as a shuttle to deliver the AAV transgene cassette inserted in an intergenomic region of the phage DNA genome. As a proof of concept, we assessed the in vivo efficacy of vector in animal models of cancer by displaying on the phage capsid the cyclic Arg-Gly-Asp (RGD-4C) ligand that binds to alphav integrin receptors specifically expressed on the angiogenic blood vessels of tumors. The ligand-directed vector was able to specifically deliver imaging and therapeutic transgenes to tumors in mice, rats, and dogs while sparing the normal organs. This chapter reviews some gene transfer strategies and the potential of the vascular-targeted AAVP vector for enhancing the effectiveness of existing systemic gene delivery and genetic-imaging technologies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2660
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Print
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-82
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Targeted systemic gene therapy and molecular imaging of cancer contribution of the vascular-targeted AAVP vector.
pubmed:affiliation
Department of Gene Therapy, Section/ Division of Infectious Diseases, Faculty of Medicine, Imperial College London, Wright-Fleming Institute, St Mary's Campus, Norfolk Place, London, United Kingdom.
pubmed:publicationType
Journal Article, Review