Super p53 for Treatment of Ovarian Cancer
Technical Report,15 Jun 2015,14 Jun 2017
University of Utah Salt Lake City United States
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In this final report, we show gene therapy using re-engineered super p53 p53-CC constructs kills some ovarian cancer cell lines in vitro, but was not superior to wild-type p53, and showed toxicity in normal cells. Combination therapy using gene therapy and chemotherapy proved to be difficult, due to the genel transfection inhibition by paclitaxel. In order to overcome these issues, a mitochondrially targeted p53 p53-MTS was used, and was found to be more potent in killing 2 different ovarian cancer cell lines superior to wt p53, and p53-CC. From this, p53-MTS will then serve as a lead construct. Technical skills gained in the proposal include cell culture, transfections, microscopy, apoptosis assays, transcriptional assays, polymer synthesis, cloning, adenoviral vector preparation, and in vivo work. Importantly, we have verified the ovarian cancer animal model and are able to create ovarian tumors in mice. Our polymer-adenovirus constructs were optimized in vitro and in vivo, and did not show gross signs of toxicity. Future studies ongoing in the lab include optimization of cancer-specific promoters to drive production of p53-MTS in cancer cells only, and testing polymer-adenovirus encoding p53-MTS in vivo, which are expected to reduce ovarian cancer tumors.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research