2016 Fiscal Year Final Research Report
Development of a novel RNA trans-splicing molecule for cancer gene therapy targeting to cancer-type organic anion transporting polypeptide 1B3
| Project/Area Number |
15K14994
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | cancer-type OATP1B3 / がん遺伝子治療 / がん |
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| Outline of Final Research Achievements |
Spliceosome-mediated RNA trans-splicing, which is mediated by an RNA trans-splicing molecule (RTM), is expected to be a promising tool for cancer gene therapy. RTM leads to trans-splicing between a target mRNA and a suicide gene (such as the herpes simplex virus thymidine kinase) to generate the suicide protein. Therefore, we aimed at development and characterization of an RTM targeting to Ct-OATP1B3 mRNA (hereafter referred to as RTM44-2), which is expressed in various cancer tissues in a cancer-specific manner. To examine the RTM44-2 functionality, we developed LS180 cells stably expressing RTM44-2 (RTM/LS), and cytotoxic assays were performed using ganciclovir (GCV). As a result. GCV significantly reduced the viability of RTM/LS cells. Furthermore, such anti-cancer effects of the RTM-GCV system was also observed in vivo xenograft models. To summarize, our results indicate that the Ct-OATP1B3-targeted gene therapy has a potential to become an effective anti-cancer therapy.
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| Free Research Field |
薬理学・薬物動態学
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