595: The Development of a Cellular Delivery System for RNA Interference Targeted to Canine Tumors

Grant Status: Closed

Grant Amount: $53,738
David J. Argyle, PhD; University of Edinburgh
July 1, 2006 - June 30, 2007

Sponsor(s): BEACON for Health, Leonberger Health Foundation, Portuguese Water Dog Club of America, Inc., Portuguese Water Dog Foundation, Versatility in Poodles, Inc.

Breed(s): -All Dogs
Research Program Area: Oncology
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Abstract

From our own studies, expression of the enzyme telomerase has emerged as a central unifying mechanism underlying the immortal phenotype of cancer cells and has thus become a candidate for targeted molecular therapies. In vitro, we have demonstrated that RNA inhibition (RNAi) using Small Interfering RNAs (siRNA) is a promising mechanism for targeting telomerase. However, the clinical development of such a therapy will rely on the parallel development of efficient delivery systems. With Canine Health Foundation support (An Investigation into Combined Molecular Approaches to Treat Hemangiosarcoma) we have developed an siRNA molecule that effectively and efficiently blocks telomerase expression. Further, we have improved efficiency of this system by incorporating this molecule in a lentiviral vector system. This project aims to expand this study to develop an effective cellular delivery system whereby this vector can be delivered systemically to cancer patients to target the primary tumor and metastatic deposits.

Publication(s)

Lund, J. R., Paoloni, M., Kurzman, I., Padilla, M., & Argyle, D. J. (2008). Inhibition of canine telomerase in vitro and in vivo using RNAi: Further development of a natural canine model for telomerase-based cancer therapies. The Veterinary Journal, 177(2), 192–197. https://doi.org/10.1016/j.tvjl.2007.09.015

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