Document Detail


Regulated expression of the interferon-beta gene in mice.
MedLine Citation:
PMID:  17637794     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A single plasmid regulated expression vector based upon a mifepristone-inducible two plasmid system, termed pBRES, has been constructed and tested in mice using murine interferon-b (mIFNb) as the transgene. The expression of mIFNb in the circulation was followed by measuring the systemic induction of IP-10, a validated biomarker for mIFNb in mice. Long-term, inducible expression of mIFNb was demonstrated following a single intramuscular (i.m.) injection of the pBRES mIFNb plasmid vector into the hind limb of mice. Induction of mIFNb expression was achieved by administration of the small molecule inducer, mifepristone (MFP). Plasmid DNA and mIFNb mRNA levels in the injected muscles correlated with mIFNb expression as monitored by IP-10 over a 3-month time period. Renewable transgene expression was achieved following repeat administration of the plasmid at 3 months following the first plasmid injection. A dose-dependent increase in expression was demonstrated by varying the amount of injected plasmid or the amount of the inducer administered to the mice. Finally, the pBRES plasmid expressing mIFNb under control of the inducer, MFP, was shown to be efficacious in a murine model of experimental allergic encephalomyelitis, supporting the feasibility of gene-based therapeutic approaches for treating diseases such as multiple sclerosis.
Authors:
R N Harkins; P Szymanski; H Petry; A Brooks; H S Qian; C Schaefer; P J Kretschmer; A Orme; P Wang; G M Rubanyi; T W Hermiston
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Publication Detail:
Type:  Journal Article     Date:  2007-07-19
Journal Detail:
Title:  Gene therapy     Volume:  15     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-18     Completed Date:  2008-04-11     Revised Date:  2010-07-29    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-11     Citation Subset:  IM    
Affiliation:
Department of Gene Technologies, Berlex Biosciences, Richmond, CA, USA. rick.harkins@bayer.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers / blood
Chemokine CXCL10 / analysis
Disease Progression
Encephalomyelitis, Autoimmune, Experimental / therapy*
Female
Gene Expression Regulation*
Gene Therapy / methods*
Genetic Vectors / administration & dosage*
Injections, Intramuscular
Interferon-beta / blood,  genetics*
Mice
Mice, Inbred Strains
Mifepristone / administration & dosage
Multiple Sclerosis / therapy
Plasmids / administration & dosage*,  analysis
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Transgenes
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Chemokine CXCL10; 0/RNA, Messenger; 77238-31-4/Interferon-beta; 84371-65-3/Mifepristone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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