2009 Fiscal Year Final Research Report
Development of AAV (adeno-associated virus) vectors and their application to cancer therapy
Project/Area Number |
17016067
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Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | Jichi Medical University |
Principal Investigator |
OZAWA Keiya Jichi Medical University, 医学部, 教授 (30137707)
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Co-Investigator(Kenkyū-buntansha) |
MIZUKAMI Horoaki 自治医科大学, 医学部, 講師 (20311938)
URABE Masashi 自治医科大学, 医学部, 講師 (40213516)
MATSUSHITA Takashi 自治医科大学, 医学部, 助教 (20343444)
OKADA Takashi 自治医科大学, 医学部, 講師 (00326828)
TSUKAHARA Tomonri 自治医科大学, 医学部, 助教 (10362120)
|
Project Period (FY) |
2005 – 2009
|
Keywords | 遺伝子 / ウイルス / 癌 / バイオテクノロジー / 遺伝子治療 |
Research Abstract |
A) Development of AAV (adeno-associated virus)-mediated cancer gene therapy : 1) Establishment of AAV vector production system using baculovirus expression vectors : AAV vectors were efficiently produced in insect cells. We developed a column chromatographic method to isolate AAV vector particles from empty capsids, which can be adaptable to large-scale production of AAV vectors. Incorporation of the AAV p5 promoter into a transgene sequence increased the efficiency of AAV vector production. 2) Basic studies of the modification of AAV vectors : Chimeric type 5 AAV vectors with type 2 VP1 had a larger amount of VP 1 in their capsids and transduced target cells in a similar manner with parent type 5 AAV vectors. 3) Basic studies of AAV vector-mediated gene transfer and the regulation of transgene expression : We established standard methods of gene transfer into muscle, liver, adipose tissue and peritoneum. A histone deacetylase inhibitor enhanced AAV vector-mediated transgene expression in tumor cells. 4) Examination of strategies for cancer gene therapy using AAV vectors : We conducted gene therapy experiments for refractory cancers (e.g. hematogenous and/or lymphogenous metastasis, and peritoneal dissemination) and showed therapeutic efficacy in tumor-bearing animals. B) Research on novel strategies for cancer gene therapy : For the treatment of refractory malignant lymphoma (B-cell non-Hodgkin lymphoma), we conducted experiments to develop a novel reinforced adoptive immuno-gene therapy using T-cells expressing a CAR (chimeric antigen receptor) targeting CD 19. We demonstrated that genetically engineered T-cells efficiently lyzed CD 19positive B-cell lymphoma cells in vitro.
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[Journal Article] Generation of adeno-associated virus vector enabling functional expression of oxytocin receptor and fluorescence marker genes using the human eIF4G internal ribosome entry site element.2009
Author(s)
Sato, K., Date, S., Aoyagi, Y., Kasahara, Y., Nawa, A., Mizukami, H., Hidema, S., Ozawa, K., Nishimori, K.
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Journal Title
Biosci. Biotechnol. Biochem. 73(9)
Pages: 2145-2148
Peer Reviewed
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[Journal Article] A convenient enzyme-linked immunosorbent assay for rapid screening of anti-adeno-associated virus neutralizing antibodies.2009
Author(s)
Ito, T., Yamamoto, S., Hayashi, T., Kodera, M., Mizukami, H., Ozawa, K., Muramatsu, S.
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Journal Title
Ann. Clin. Biochem. 46(Pt6)
Pages: 508-510
Peer Reviewed
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[Journal Article] Scalable purification of adeno-associated virus serotype 1 (AAV1) and AAV8 vectors, using dual ion-exchange adsorptive membranes.2009
Author(s)
Okada, T., Nonaka-Sarukawa, M., Uchibori, R., Kinoshita, K., Hayashita-Kinoh, H., Nitahara-Kasahara, Y., Takeda, S., Ozawa, K.
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Journal Title
Hum. Gene Ther. 20(9)
Pages: 1013-1021
Peer Reviewed
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[Journal Article] Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapy.2009
Author(s)
Uchibori, R., Okada, T., Ito, T., Urabe, M., Mizukami, H., Kume, A., Ozawa, K.
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Journal Title
J. Gene Med. 11
Pages: 373-381
Peer Reviewed
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[Journal Article] Overexpression of PTEN in ovarian cancer cells suppresses i. p. dissemination and extends survival in mice.2008
Author(s)
Takei, Y., Saga, Y., Mizukami, H., Takayama, T., Ohwada, M., Ozawa, K., Suzuki, M.
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Journal Title
Mol. Cancer. Ther. 7(3)
Pages: 704-711
Peer Reviewed
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[Journal Article] Adeno-associated virus vector-mediated systemic interleukin-10 expression ameliorates hypertensive organ damage in Dahl salt-sensitive rats.2008
Author(s)
Nonaka-Sarukawa, M., Okada, T., Ito, T., Yamamoto, K., Yoshioka, T., Nomoto, T., Hojo, Y., Shimpo, M., Urabe, M., Mizukami, H., Kume, A., Ikeda, U., Shimada, K., Ozawa, K.
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Journal Title
J Gene Med. 10(4)
Pages: 368-374
Peer Reviewed
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[Journal Article] Protection against aminoglycoside-induced ototoxicity by regulated AAV vector-mediated GDNF gene transfer into the cochlea.2008
Author(s)
Liu, Y., Okada, T., Shimazaki, K., Sheykholeslami, K., Nomoto, T., Muramatsu, S., Mizukami, H., Kume, A., Xiao, S., Ichimura, K., Ozawa, K.
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Journal Title
Mol. Ther. 16(3)
Pages: 474-480
Peer Reviewed
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[Journal Article] Interleukin-10 expression mediated by an adeno-associated virus vector prevents monocrotaline-induced pulmonary arterial hypertension in rats.2007
Author(s)
Ito, T., Okada, T., Miyashita, H., Nomoto, T., Nonaka-Sarukawa, M., Uchibori, R., Maeda, Y., Urabe, M., Mizukami, H., Kume, A., Takahashi, M., Ikeda, U., Shimada, K., Ozawa, K.
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Journal Title
Circ. Res. 101
Pages: 734-741
Peer Reviewed
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[Journal Article] Adeno-associated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats.2007
Author(s)
Ito, T., Okada, T., Mimuro, J., Miyashita, H., Uchibori, R., Urabe, M., Mizukami, H., Kume, A., Takahashi, M., Ikeda, U., Sakata, Y., Shimada, K., Ozawa, K.
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Journal Title
Hypertension 50
Pages: 531-536
Peer Reviewed
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[Journal Article] Transforming activity of purinergic receptor P2Y, G protein coupled, revealed by retroviral expression screening.2007
Author(s)
Fujiwara, S., Yamashita, Y., Choi, Y.L., Watanabe, H., Kurashina, K., Soda, M., Enomoto, M., Hatanaka, H., Takada, S., Ozawa, K., Mano, H.
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Journal Title
Leuk. Lymphoma. 48
Pages: 978-986
Peer Reviewed
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[Journal Article] Interferon-gamma and NF-kappaB mediate nitric oxide production by mesenchymal stromal cells.2007
Author(s)
Oh, I., Ozaki, K., Sato, K., Meguro, A., Tatara, R., Hatanaka, K., Nagai, T., Muroi, K., Ozawa, K.
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Journal Title
Biochem. Biophys. Res. Commun. 355
Pages: 956-962
Peer Reviewed
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[Journal Article] Prevention of diabetic retinopathy by intraocular soluble Flt-1 gene transfer in a spontaneously diabetic rat model.2007
Author(s)
Ideno, J., Mizukami, H., Kakehashi, A., Saito, Y., Okada, T., Urabe, M., Kume, A., Kuroki, M., Kawakami, M., Ishibashi, S., Ozawa, K.
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Journal Title
Int. J. Mol. Med. 19
Pages: 75-79
Peer Reviewed
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[Journal Article] Nitric oxide plays a critical role in suppression of T cell proliferation by mesenchymal stem cells.2007
Author(s)
Sato, K., Ozaki, K., Oh, I., Meguro, A., Hatanaka, K., Nagai, T., Muroi, K., Ozawa, K.
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Journal Title
Peer Reviewed
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[Journal Article] Suppression of ovarian cancer by muscle-mediated expression of soluble VEGFR-1/Flt-1 using adeno-associated virus serotype 1-derived vector.2006
Author(s)
Takei, Y., Mizukami, H., Saga, Y., Yoshimura, I., Hasumi, Y., Takayama, T., Kohno, T., Matsushita, T., Okada, T., Kume, A., Suzuki, M., Ozawa, K.
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Journal Title
Int. J. Cancer 120
Pages: 278-284
Peer Reviewed
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[Journal Article] Adipose tissue as a novel target for in vivo gene transfer by adeno-associated viral vectors.2006
Author(s)
Mizukami, H., Mimuro, J., Ogura, T., Okada, T., Urabe, M., Kume, A., Sakata, Y., Ozawa, K.
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Journal Title
Hum. Gene Ther. 17
Pages: 921-928
Peer Reviewed
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[Journal Article] Phenotype correction of hemophilia A mice with adeno-associated virus vectors carrying the B domain-deleted canine factor VIII gene.2006
Author(s)
Ishiwata, A., Mimuro, J., Kashiwakura, Y., Niimura, M., Takano, K., Ohmori, T., Madoiwa, S., Mizukami, H., Okada, T., Naka, H., Yoshioka, A., Ozawa, K., Sakata, Y.
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Journal Title
Thromb. Res. 118
Pages: 627-635
Peer Reviewed
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[Journal Article] Utility of intraperitoneal administration as a route of AAV serotype 5 vector-mediated neonatal gene transfer.2006
Author(s)
Ogura, T., Mizukami, H., Mimuro, J., Madoiwa, S., Okada, T., Matsushita, T., Urabe, M., Kume, A., Hamada, H., Yoshikawa, H., Sakata, Y., Ozawa, K.
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Journal Title
Gene Med. 8
Pages: 990-997
Peer Reviewed
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[Journal Article] rAAV-mediated shRNA ameliorated 6 neuropathology in Huntington disease model mouse. Biochem.2006
Author(s)
Machida, Y., Okada, T., Kurosawa, M., Oyama, F., Ozawa, K., Nukina, N.
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Journal Title
Biophys. Res. Commun. 343
Pages: 190-197
Peer Reviewed
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[Journal Article] Removal of empty capsids from type 1 adeno-associated virus vector stocks by anion-exchange chromatography potentiates transgene expression.2006
Author(s)
Urabe, M., Xin, K.Q., Obara, Y., Nakakura, T., Mizukami, H., Kume, A., Okuda, K., Ozawa, K.
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Journal Title
Mol. Ther. 13
Pages: 823-828
Peer Reviewed
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[Journal Article] Scalable generation of high-titer recombinant adeno-associated virus type 5 in insect cells.2006
Author(s)
Urabe, M., Nakakura, T., Xin, K.Q., Obara, Y., Mizukami, H., Kume, A., Kotin, R.M., Ozawa, K.
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Journal Title
J. Virol. 80
Pages: 1874-1885
Peer Reviewed
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[Journal Article] A histone deacetylase inhibitor enhances recombinant adeno-associated virus-mediated gene expression in tumor cells.2006
Author(s)
Okada, T., Uchibori, R., Iwata-Okada, M., Takahashi, M., Nomoto, T., Nonaka-Sarukawa, M., Ito, T., Liu, Y., Mizukami, H., Kume, A., Kobayashi, E., Ozawa, K.
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Journal Title
Mol. Ther. 13
Pages: 738-746
Peer Reviewed
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[Journal Article] Viral-mediated temporally controlled dopamine production in a rat model of Parkinson disease.2006
Author(s)
Li, X.G., Okada, T., Kodera, M., Nara, Y., Takino, N., Muramatsu, C., Ikeguchi, K., Urano, F., Ichinose, H., Metzger, D., Chambon, P., Nakano, I., Ozawa, K., Muramatsu, S.
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Journal Title
Mol. Ther. 13
Pages: 160-166
Peer Reviewed
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[Journal Article] Transforming activity of the lymphotoxin-beta receptor revealed by expression screening.2005
Author(s)
Fujiwara, S., Yamashita, Y., Choin Y.L., Wada, T., Kaneda, R., Takada, S., Maruyama, Y., Ozawa, K., Mano, H.
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Journal Title
Biochem. Biophys. Res. Commun. 338
Pages: 1256-1262
Peer Reviewed
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[Journal Article] Large-scale production of recombinant viruses by use of a large culture vessel with active gassing.2005
Author(s)
Okada, T., Nomoto, T., Yoshioka, T., Nonaka-Sarukawa, M., Ito, T., Ogura, T., Iwata-Okada, M., Uchibori, R., Shimazaki, K., Mizukami, H., Kume, A., Ozawa, K.
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Journal Title
Hum. Gene Ther. 16
Pages: 1212-1218
Peer Reviewed
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[Journal Article] Specific and efficient transduction of cochlear inner hair cells with recombinant adeno-associated virus type 3 vector.2005
Author(s)
Liu, Y., Okada, T., Sheykholeslami, K., Shimazaki, K., Nomoto, T., Muramatsu, S., Kanazawa, T., Takeuchi, K., Ajalli, R., Mizukami, H., Kume, A., Ichimura, K., Ozawa, K.
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Journal Title
Mol. Ther. 12
Pages: 725-733
Peer Reviewed
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[Journal Article] Repair of articular cartilage defect by autologous transplantation of basic fibroblast growth factor gene-transduced chondrocytes with adeno-associated virus vector.2005
Author(s)
Yokoo, N., Saito, T., Uesugi, M., Kobayashi, N., Xin, K.Q., Okuda, K., Mizukami, H., Ozawa, K., Koshino, T.
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Journal Title
Arthritis Rheum. 52
Pages: 164-170
Peer Reviewed
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[Journal Article] Efficient and stable Sendai virus-mediated gene transfer into primate embryonic stem cells with pluripotency preserved.2005
Author(s)
Sasaki, K., Inoue, M., Shibata, H., Ueda, Y., Muramatsu, S., Okada, T., Hasegawa, M., Ozawa, K., Hanazono, Y.
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Journal Title
Gene Ther. 12
Pages: 203-210
Peer Reviewed