Linked Life Data

17203206

Source:http://linkedlifedata.com/resource/pubmed/id/17203206

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-4
pubmed:abstractText
Gene therapy for congenital protein deficiencies requires lifelong expression of a deficient protein. Current gene therapy approaches preferentially employ the strong cytomegalovirus (CMV) promoter/enhancer or its derivative CAG promoter; however, these promoters provide only temporary transgene expression. To create a promoter that enables long-lasting expression in muscle, hybrid promoters were constructed by coupling the muscle creatine kinase (MCK) enhancer to various strong promoters for enhancement of tissue specificity and improved transcriptional activity. A hybrid promoter containing the MCK enhancer and the simian virus 40 promoter (MCK/SV40 promoter) yielded long-term (>6 months) expression of a human secretory alkaline phosphatase (huSEAP) reporter gene following electrotransfer of the plasmid into mice, whereas expression using a conventional CMV or CAG promoter faded away within a few weeks. To explore the mechanism behind the sustained expression obtained with the MCK/SV40 promoter, mice were immunized with a LacZ expression plasmid driven by MCK/SV40 or a conventional promoter. Minimal cellular and humoral responses to LacZ were observed in MCK/SV40 promoter-treated animals, and mouse SEAP gene expression in vivo was successfully maintained by both the MCK/SV40 and conventional promoters. These results suggest that the lower immunogenicity of the MCK/SV40 promoter contributed to long-lasting gene expression in mice. Therefore, the MCK/SV40 promoter may provide the basis for development of an effective transgene expression cassette for treatment of congenital protein deficiencies in which therapeutic proteins are recognized as foreign by the host immune system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1107-3756
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
309-15
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Muscle creatine kinase/SV40 hybrid promoter for muscle-targeted long-term transgene expression.
pubmed:affiliation
Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. takesita@yokohama-cu.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't