Linked Life Data

10856307

Source:http://linkedlifedata.com/resource/pubmed/id/10856307

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2000-10-27
pubmed:abstractText
To date, no gene transfer vector has produced prolonged gene expression following a single intravenous injection and then efficiently re-expressed the delivered gene following repeated systemic injection into immunocompetent hosts. To overcome these limitations, a gene therapy regimen using non-replicating Epstein-Barr virus (EBV)-based expression plasmids was developed. One plasmid contains the FR (EBV family of repeats) sequence and the expressed gene. The other encodes Epstein-Barr nuclear antigen 1 (EBNA-1), but lacks FR. Although unable to replicate in mice, intravenous co-injection of EBV-based plasmids in cationic liposome-DNA complexes (CLDCs) substantially prolonged luciferase gene expression. The use of a two-vector system limited host exposure to the EBNA-1 gene product. Furthermore, this EBV-based vector system could be intravenously re-injected multiple times into immunocompetent mice without loss of transfection efficiency. Use of this vector system significantly improved the therapeutic efficacy of the biologically important human granulocyte colony-stimulating factor gene. Delivery of the human granulocyte colony-stimulating factor gene in EBV-based plasmids increased circulating white blood counts for at least 2 months following a single CLDC-based intravenous co-injection. Conversely, white blood counts were never elevated following injection of CLDCs lacking EBV-derived elements. Thus, this EBV-based plasmid vector system both markedly prolongs gene expression at therapeutic levels and efficiently and repeatedly re-transfects immunocompetent hosts. These properties of EBV-based plasmid vectors appear to be due, at least in part, to the documented abilities of the EBNA-1 protein both to retain FR-containing DNA intracellularly and within the nucleus and to block anti-EBNA-1 cytotoxic T cell responses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30408-16
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10856307-Animals, pubmed-meshheading:10856307-DNA, Viral, pubmed-meshheading:10856307-Drug Carriers, pubmed-meshheading:10856307-Epstein-Barr Virus Nuclear Antigens, pubmed-meshheading:10856307-Female, pubmed-meshheading:10856307-Gene Expression, pubmed-meshheading:10856307-Gene Therapy, pubmed-meshheading:10856307-Genes, Reporter, pubmed-meshheading:10856307-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:10856307-Herpesvirus 4, Human, pubmed-meshheading:10856307-Humans, pubmed-meshheading:10856307-Injections, Intravenous, pubmed-meshheading:10856307-Liposomes, pubmed-meshheading:10856307-Luciferases, pubmed-meshheading:10856307-Mice, pubmed-meshheading:10856307-Mice, Inbred Strains, pubmed-meshheading:10856307-Plasmids, pubmed-meshheading:10856307-Repetitive Sequences, Nucleic Acid, pubmed-meshheading:10856307-Virus Replication
pubmed:year
2000
pubmed:articleTitle
Non-replicating Epstein-Barr virus-based plasmids extend gene expression and can improve gene therapy in vivo.
pubmed:affiliation
California Pacific Medical Research Institute, San Francisco, California 94115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't