2009 Fiscal Year Final Research Report
Development of adenovirus vectors and expression systems aiming cancer therapy
| Project/Area Number |
17016014
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SAITO Izumu The University of Tokyo, 医科学研究所, 教授 (70158913)
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| Co-Investigator(Kenkyū-buntansha) |
KANEGAE Yumi 東京大学, 医科学研究所, 助教 (80251453)
KONDO Saki 東京大学, 医科学研究所, 助教 (80451871)
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| Project Period (FY) |
2005 – 2009
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| Keywords | アデノウイルスベクター / 遺伝子治療 / 部位特異的組換え酵素 / Cre / loxP / FLP / FRT |
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| Research Abstract |
Aiming gene therapy for "unvisible cancer" such as disseminating or transferring malignant microtumors, we developed a "single-type, cancer-specific adenovirus vector with high-level expression" possessing cell specificity and high expression efficiency. For addition of high specificity, we used a cancer-specific promoter. Construction methods of two vector systems, a "stuffer-deletion type" and a novel "excisional-expression type", were established. Each system contains two expression units: a "switch unit" expressing Cre under the control of a cell-specific promoter with very low activity, and a "target unit" expressing under the control of very high activity depending on the Cre activity. During the process, it was found that Cre was expressed at a leak and influenced on production of the purpose vector. Therefore, we produced and screened dominant negatives and shRNA against Cre. Using them, we succeeded in the development of high-purity production of the "excisional-expression type" vector. Because the vector established here showed high expression efficiency selectively to cancer cells, we then established a model muse system for examining effective treatment to disseminated cancers. In addition, we also analyzed RMCE (recombinase-mediated cassette exchange) reaction of Cre and FLP, and succeeded in establishment of novel production method, which enabled us to produce many vectors simultaneously.
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[Journal Article] An animal model of preclinical diagnosis of pancreatic ductal adenocarcinomas.2009
Author(s)
Fukamachi K, Tanaka H, Hagiwara Y, Ohara H, Joh T, Iigo M, Alexander, D. B, Xu J, Long N, Takigahira M, Yanagihara K, Hino O, Saito I., Tsuda H.
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Journal Title
Biochem Biophys Res Commun. 390
Pages: 636-641
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[Journal Article] α-Catenin is essential in intestinal adenoma formation.2007
Author(s)
Shibata H, Takano H, Ito M, Shioya H, Hirota M, Matsumoto H, Kakudo Y, Ishioka C, Akiyama T, Kanegae Y, Saito I, Noda T.
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Journal Title
Proc Natl Acad Sci U S A. 104
Pages: 18199-204
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[Journal Article] Ductal origin of pancreatic adenocarcinomas induced by conditional activation of a human Ha-ras oncogene in rat pancreas.2006
Author(s)
Ueda S, Fukamachi K, Matsuoka Y, Takasuka N, Takeshita F, Naito A, Iigo M, Alexander DB, Moore MA, Saito I, Ochiya T, Tsuda H.
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Journal Title
Carcinogenesis. 27
Pages: 2497-2510
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[Journal Article] Diverse DNA methylation statuses at alternative promoters of human genes in various tissues.2006
Author(s)
Cheong J, Yamada Y, Yamashita R, Irie T, Kanai A, Wakaguri H, Nakai K, Ito T, Saito I, Sugano S, Suzuki Y.
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Journal Title
DNA Research. 13
Pages: 155-167
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[Journal Article] Prolonged skin allograft survival by IL-10 gene-introduced CD4 T cell administration2005
Author(s)
Miyamoto T, Kaneko T, Yamashita M, Tenda Y, Inami M, Suzuki A, Ishii S, Kimura M, Hashimoto K, Shimada H, Yahata H, Ochiai T, Saito I, DeGregori J, Nakayama T.
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Journal Title
Int Immunol. 17
Pages: 759-768
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[Journal Article] K. A database of recombinant viruses and recombinant viral vectors available from the RIKEN DNA bank.2005
Author(s)
Ugai H, Murata T, Nagamura Y, Ugawa Y, Suzuki E, Nakata H, Kujime Y, Inamoto S, Hirose M, Inabe K, Terashima M, Yamasaki T, Liu B, Nakade K, Pan J, Kimura M, Saito I, Hamada H, Obata Y, Yokoyama K.
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Journal Title
J Gene Med 7
Pages: 1148-1157
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