Linked Life Data

18673152

Source:http://linkedlifedata.com/resource/pubmed/id/18673152

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-8-4
pubmed:abstractText
Gene therapy is a growing topic in the medical arena. Since the safety system of gene therapy has not been sufficiently established, its clinical use is limited. Recently, we developed a cell-specific gene regulation system based on a new concept, D-RECS, or Drug and Gene Delivery System Responding to Cellular Signals. We hoped here to apply this D-RECS concept to gene therapy for virus infections. In the present study, we report the design, synthesis and characterization of the functional polymers, which are able to discriminate normal and human immunodeficiency virus type 1 (HIV-1) infected cells. In the D-RECS concept, certain intracellular signals, which are extraordinary activated in the target disease cells specifically, are used as a trigger to activate a transgene expression. Thus, we paid attention to HIV protease as a target signal in this case, because HIV protease is essential for the proliferation of HIV. This protease is therefore an indicator of HIV infection. Two types of polymers were designed and synthesized using methacryloyl peptide and acrylamide with radical copolymerization as a functional gene regulator. The grafted peptide possesses a cationic protein transduction domain (PTD) sequence of HIV-Tat protein, GRKKRRQRRRPPQ for cell permeation, which are connected with polyacrylamide backbone via a consensus substrate sequence for HIV protease, SQNY/PIVQ. At first, the polymers were evaluated to see whether they possess DNA binding ability and HIV protease responsibility using gel retardation assay. The results suggested that a polymer could form a stable complex with DNA and release the DNA specifically responding to HIV protease activity. Furthermore, it was shown that this controlled release of DNA by the HIV protease signal-responsive intelligent polymer actually regulated the gene expression in the cell-free system. This system would be a useful tool for gene therapy in HIV infection, and this methodology will be applicable if the cationic peptide is replaced by another virus-specific protease, which is critical for the replication of a corresponding virus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1573-4064
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
386-91
pubmed:dateRevised
2008-9-26
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Drug delivery system based on responses to an HIV infectious signal.
pubmed:affiliation
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't