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Rapamycin control of transgene expression from a single AAV vector in mouse salivary glands

Gene Therapy volume 13, pages 187–190 (2006)Cite this article

Abstract

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 (1010 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.

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Acknowledgements

We thank Dr Martin Kriete (NIDCR, Animal Facility) for his invaluable help with animal studies and Mr Richard Hayward and Ms Kathleen Bolland (NIDCR, Sequencing Core Facility) for their assistance in determining vector sequence.

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Author notes

  1. J Wang

    Present address: School of Dentistry, Dental Research Institute, UCLA, Los Angeles, CA, USA

Authors and Affiliations

  1. Gene Therapy and Therapeutics Branch, NIDCR, NIH, DHHS, Bethesda, MD, USA

    J Wang, A Voutetakis, B M Lodde, F Mineshiba & B J Baum

  2. ACU, NIDCR, NIH, DHHS, Bethesda, MD, USA

    M Papa

  3. ARIAD Gene Therapeutics, Cambridge, MA, USA

    V M Rivera & T Clackson

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  1. J Wang
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  2. A Voutetakis
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  4. V M Rivera
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Wang, J., Voutetakis, A., Papa, M. et al. Rapamycin control of transgene expression from a single AAV vector in mouse salivary glands. Gene Ther 13, 187–190 (2006). https://doi.org/10.1038/sj.gt.3302647

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