Document Detail

Rapamycin control of transgene expression from a single AAV vector in mouse salivary glands.
MedLine Citation:
PMID:  16177817     Owner:  NLM     Status:  MEDLINE    
Salivary glands (SGs) appear to be a useful target site for gene therapeutics. The ability to control transgene expression is essential for clinical application. Previously, in a proof-of-concept study, we have shown that the rapamycin-inducible transcriptional regulation system can regulate protein expression after adenoviral-mediated gene transfer to SGs. To evaluate the potential ability to utilize this regulatory system for long-term control of transgene expression in this tissue, we employed a 'third generation', single adenoassociated serotype 2 viral (AAV2) vector encoding human erythropoietin (hEPO) under the control of a rapamycin-inducible promoter. The vector, rAAV-TF2.3-hEPO (10(10) particles/animal), was delivered to mouse SGs. No detectable increase in serum hEPO or hematocrit levels was observed in the absence of rapamycin administration. However, rapamycin induced elevation of serum hEPO levels, as well as concomitant hematocrit changes, that were dose-dependent, completely reversible, and relatively stable over the course of this study (6 months), with no appreciable change in rapamycin responsiveness. Our results suggest that the rapamycin transcriptional regulation system delivered in a single AAV2 vector to SGs may be valuable for systemic protein replacement applications.
J Wang; A Voutetakis; M Papa; V M Rivera; T Clackson; B M Lodde; F Mineshiba; B J Baum
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Gene therapy     Volume:  13     ISSN:  0969-7128     ISO Abbreviation:  Gene Ther.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-06     Completed Date:  2006-05-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  187-90     Citation Subset:  IM    
Gene Therapy and Therapeutics Branch, NIDCR, NIH, DHHS, Bethesda, MD 20892, USA.
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MeSH Terms
Adenoviridae / genetics*
Dose-Response Relationship, Drug
Erythropoietin / blood,  genetics*,  pharmacokinetics
Gene Expression
Gene Expression Regulation*
Gene Therapy / methods*
Genetic Vectors / administration & dosage*,  genetics
Immunosuppressive Agents / therapeutic use*
Mice, Inbred BALB C
Salivary Glands / metabolism*
Sirolimus / therapeutic use*
Time Factors
Transduction, Genetic
Reg. No./Substance:
0/Immunosuppressive Agents; 11096-26-7/Erythropoietin; 53123-88-9/Sirolimus

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