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首页> 美国政府科技报告 >Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy.
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Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy.

机译：双重选择方法实现卵巢癌基因治疗毒素基因的特异性表达。

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Gene therapy is a novel treatment modality which offers great potential for the control of carcinoma of the ovary. The efficacy of such approaches, however, is currently limited due to the inability of available gene delivery vehicles (vectors) to achieve efficient and selective gene transfer to target tumor cells. Proposed herein is a strategy to modify one candidate vector, recombinant adenovirus, such that it embodies the requisite properties of efficacy and specificity required for ovarian cancer gene therapy. This approach is based on targeting the delivered anti-cancer gene to tumor via two complimentary approaches. This strategy is based upon restricting the expression of the anti-cancer gene exclusively to ovarian cancer tumor cells ('transductional targeting') plus directing the binding of the viral vector particle exclusively to tumor cells ('transductional targeting').This 'double targeting' approach is highly novel. We have advanced this double targeting approach in the current period. In the first regard, we have improved the infectivity of adenovirus (Ad) for ovarian cancer targets via a knob 'switch' method exploiting fiber knobs of canine and ovine Ad fiber knobs. In the second instance, we have defined optimized tumor selective promoters for ovarian cancer (TSPs). In this period we have shown the utility of both of these modifications to improve adenovirus targeting for ovarian tumor cells in vitro and in vivo. These studies have provided the framework for testing our overall concept in the future funding period, for ascertaining therapeutic gains of double targeting in murine models of carcinoma of the ovary.

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