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Targeting the RNA component of Telomerase Through RNA Interference and the Development of Vector Delivery Systems
Author(s) -
Paoloni M.,
Gunderman J. R.,
Estelle L. N.,
Padilla M.,
Argyle D. J.
Publication year - 2005
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/j.1476-5810.2005.0064d.x
Subject(s) - rna interference , telomerase reverse transcriptase , telomerase , rna , small interfering rna , reverse transcriptase , telomerase rna component , biology , microbiology and biotechnology , small hairpin rna , rna silencing , transfection , viral vector , cancer research , cell culture , genetics , gene , recombinant dna
From studies on cellular senescence and cancer, Telomerase has emerged as a near universal marker of malignancy which gives rise to the immortal phenotype of cancer. The Telomerase enzyme is composed minimally of an RNA template component and a, catalytic component, reverse transcriptase. We have previously demonstrated that RNA interference can be used to block the reverse transcriptase component at the mRNA level. In this study we used the same RNAi technology to target the RNA component, with the overall goal of improving the efficiency of cell killing. Three simple interfering RNA molecules (siRNA) targeted to the canine telomerase RNA component were generated. Simple transfection studies in telomerase positive canine cells (HSA SB) demonstrated rapid telomerase inhibition and cell killing when compared to control cells. Using the template design of one of the siRNA molecules, two vector systems (adenovirus and lentivirus) were constructed. Cell transduction experiments demonstrated these viral technologies as efficient delivery vehicles. These studies demonstrate the efficiency of RNAi technologies and offer the development of vector systems for in vivo cancer therapy.