Linked Life Data

15177892

Source:http://linkedlifedata.com/resource/pubmed/id/15177892

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-4
pubmed:abstractText
Recombinant adeno-associated virus (rAAV) receptor binding, endocytosis, nuclear trafficking and second strand gene conversion have been described as potential rate-limiting steps in rAAV type-2 (rAAV-2) transduction. Several strategies have been developed to enhance rAAV-2 intracellular trafficking and gene conversion in an attempt to increase the efficiency of this virus as a gene therapy vector. To this end, the current study has investigated novel methods for augmenting rAAV transduction by enhancing endocytosis of rAAV-2. A selective trypsinization assay demonstrated that the abundance of internalized rAAV ssDNA was increased only in cells treated with both pyrrolidinedithiocarbonate (PDTC) and a genotoxic agent. Treating cells with each of these agents alone had no effect on rAAV endocytosis in comparison to controls. To investigate the mechanisms of this synergistic effect on rAAV transduction, the involvement of Rac1 protein was evaluated. Inhibition of the Rac1 pathway by expression of a dominant negative mutant of Rac1 (N17Rac1) decreased rAAV transduction. In contrast, expression of a dominant active form of Rac1 (V12Rac1) alone mimicked the up-regulated response seen in the presence of PDTC and genotoxic agents. These studies provide potential insights into the importance of the Rac1 pathway to enhance uptake of rAAV-2.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0168-1702
pubmed:author
pubmed:issnType
Print
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Novel approaches to augment adeno-associated virus type-2 endocytosis and transduction.
pubmed:affiliation
The Human Gene Therapy Unit of Akdeniz University, Faculty of Medicine, Antalya, 07070 Turkey.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't