Journal article

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

Abstract

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..

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