Sequence-Related Off-Target Effect of Dz13 Against Human Tumor Cells and Safety in Adult and Fetal Mice Following Systemic Administration
Crispin R Dass, Peter FM Choong
Oligonucleotides | MARY ANN LIEBERT INC | Published : 2010
The oligonucleotide Dz13, a DNA enzyme that cleaves c-Jun mRNA, is capable of inhibiting various model tumors in mice. However, to date, a thorough examination of its target specificity in tumor cells has not been performed. In addition, an evaluation of its safety in a mammalian whole organism system has not been carried out. Dz13 mutated oligonucleotides were designed and tested in a proliferation assay. Dz13 was also tested for its safety in vivo when administered intravenously in a bolus dose, or systemically in an in utero assay. While Dz13 down-regulated target gene (c-Jun) expression in human tumor cells, c-Jun siRNA failed to cause cell growth inhibition. Furthermore, alteration of c..View full abstract
We thank Maya Kansara for assistance with hematology and Levon Khachigian for Dz13 and Scr. This study was supported by funds from St. Vincent's Hospital Melbourne (Orthopaedics Department funds). The authors wish to dedicate this article to the memory of the late Rod Walsh, part of our research support team at SVH.