Development of oncolytic RNA virus sensitive to ganciclovir

• Project/Area Number: 26430155
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Chiba University
• Principal Investigator: SHIRASAWA Hiroshi 千葉大学, 大学院医学研究院, 教授 (00216194)
• Co-Investigator(Kenkyū-buntansha): 齋藤 謙悟 千葉大学, 大学院医学研究院, 講師 (70451755) ; 菅波 晃子 千葉大学, 大学院医学研究院, 助教 (10527922)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍融解ウイルス / ガンシクロビル / RNAウイルス / HSV tk

Outline of Final Research Achievements

An RNA virus, SIN, is an oncolytic virus, which cause no integration of viral genome into chromosome, specific infection and proliferation in cancer cells. In this study, to improve the safety of SIN as an oncolytic virus, we developed a SIN that expresses herpesvirus tk gene and is sensitive to anti-herpesvirus drug ganciclovir (GCV).
A recombinant SIN, SINtkGFPmE2, which have chimera gene of tk and GFP between capsid gene (C) and envelope protein gene (E2) mutated in 1 amino acid, was the most stable among recombinants we constructed. The SINtkGFPmE2 was sensitive to GCV and the proliferation was inhibited.

Research Products

• [Journal Article] Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB (2016)
  • Author(s): Wu S, Kanda T, Nakamoto S, Jiang X, Nakamura M, Sasaki R, Haga Y, Shirasawa H, Yokosuka O.
  • Journal Title: Int J Mol Med. Volume: 38 Issue: 2 Pages: 475-481
  • DOI: 10.3892/ijmm.2016.2643
  • Peer Reviewed / Open Access
• [Journal Article] Hepatitis C virus genotypes in Myanmar (2016)
  • Author(s): Win NN, Kanda T, Nakamoto S, Yokosuka O, Shirasawa H.
  • Journal Title: World J Gastroenterol. Volume: 22 Issue: 27 Pages: 6095-6099
  • DOI: 10.3748/wjg.v22.i27.6095
  • Peer Reviewed / Open Access
• [Journal Article] Feasibility of viral dust infection via air movement and dispersion of dried viral particles from the floor (2016)
  • Author(s): Mori K, Onuki A, Kanou F, Akiba T, Hayashi Y, Shirasawa H, Sadamasu K.
  • Journal Title: J Med Virol. Volume: 89 Issue: 5 Pages: 931-935
  • DOI: 10.1002/jmv.24710
  • Peer Reviewed / Open Access
• [Journal Article] Free fatty acids or high-concentration glucose enhances hepatitis A virus replication in association with a reduction in glucose-regulated protein 78 expression (2016)
  • Author(s): Nan Nwe Win, Tatsuo Kanda, Masato Nakamura, Shingo Nakamoto, Hiroaki Okamoto, Osamu Yokosuka, Hiroshi Shirasawa
  • Journal Title: Biochem Biophys Res Commun. Volume: S0006-291X Issue: 1 Pages: 32124-32126
  • DOI: 10.1016/j.bbrc.2016.12.080
  • Peer Reviewed / Open Access
• [Journal Article] Possible Involvement of Hepatitis B Virus Infection of Hepatocytes in the Attenuation of Apoptosis in Hepatic Stellate Cells. (2016)
  • Author(s): Sasaki R, Kanda T, Nakamura M, Nakamoto S, Haga Y, Wu S, Shirasawa H, Yokosuka O.
  • Journal Title: PLoS One. Volume: 11 Issue: 1 Pages: 1-17
  • DOI: 10.1371/journal.pone.0146314
  • Peer Reviewed / Open Access
• [Journal Article] Liposomally formulated phospholipid-conjugated indocyanine green for intra-operative brain tumor detection and resection. (2015)
  • Author(s): Suganami A, Iwadate Y, Shibata S, Yamashita M, Tanaka T, Shinozaki N, Aoki I, Saeki N, Shirasawa H, Okamoto Y, Tamura Y.
  • Journal Title: Int J Pharm. Volume: 496 Issue: 2 Pages: 401-406
  • DOI: 10.1016/j.ijpharm.2015.10.001
  • Peer Reviewed / Open Access
• [Journal Article] The sirtuin inhibitor sirtinol inhibits hepatitis A virus (HAV) replication by inhibiting HAV internal ribosomal entry site activity. (2015)
  • Author(s): Kanda T, Sasaki R, Nakamoto S, Haga Y, Nakamura M, Shirasawa H, Okamoto H, Yokosuka O.
  • Journal Title: Biochem Biophys Res Commun. Volume: 466 Issue: 3 Pages: 567-571
  • DOI: 10.1016/j.bbrc.2015.09.083
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Hepatitis C Virus Genotype 1b Core and NS5A Mutations on Response to Peginterferon Plus Ribavirin Combination Therapy. (2015)
  • Author(s): Nakamoto S, Imazeki F, Arai M, Yasui S, Nakamura M, Haga Y, Sasaki R, Kanda T, Shirasawa H, Yokosuka O.
  • Journal Title: Int J Mol Sci. Volume: 16 Issue: 9 Pages: 21177-21190
  • DOI: 10.3390/ijms160921177
  • Peer Reviewed / Open Access
• [Journal Article] Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain. (2015)
  • Author(s): Takenouchi A, Saito K, Saito E, Saito T, Hishiki T, Matsunaga T, Isegawa N, Yoshida H, Ohnuma N, Shirasawa H.
  • Journal Title: Pediatr Surg Int. Volume: 31 Issue: 12 Pages: 1151-1159
  • DOI: 10.1007/s00383-015-3784-y
  • Peer Reviewed / Open Access
• [Journal Article] Association between hepatitis B virus and MHC class I polypeptide-related chain A in human hepatocytes derived from human-mouse chimeric mouse liver. (2015)
  • Author(s): Sasaki R, Kanda T, Wu S, Nakamoto S, Haga Y, Jiang X, Nakamura M, Shirasawa H, Yokosuka O.
  • Journal Title: Biochem Biophys Res Commun. Volume: 464 Issue: 4 Pages: 1192-1195
  • DOI: 10.1016/j.bbrc.2015.07.102
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antiviral therapies for chronic hepatitis C virus infection with cirrhosis. (2015)
  • Author(s): Nakamoto S, Kanda T, Shirasawa H, Yokosuka O.
  • Journal Title: World J Hepatol. Volume: 7 Issue: 8 Pages: 1133-1141
  • DOI: 10.4254/wjh.v7.i8.1133
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of cell cycle progression by Sindbis virus infection. (2015)
  • Author(s): Yi R, Saito K, Isegawa N, Shirasawa H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 462 Issue: 4 Pages: 426-432
  • DOI: 10.1016/j.bbrc.2015.04.148
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells. (2015)
  • Author(s): Jiang X, Kanda T, Nakamoto S, Saito K, Nakamura M, Wu S, Haga Y, Sasaki R, Sakamoto N, Shirasawa H, Okamoto H, Yokosuka O
  • Journal Title: Biochem Biophys Res Commun Volume: 印刷中 Issue: 4 Pages: 908-912
  • DOI: 10.1016/j.bbrc.2015.02.058
  • Peer Reviewed / Open Access
• [Journal Article] Reactivation of Hepatitis B Virus in Hematopoietic Stem Cell Transplant Recipients in Japan: Efficacy of Nucleos(t)ide Analogues for Prevention and Treatment. (2014)
  • Author(s): Nakamoto S, Kanda T, Nakaseko C, Sakaida E, Ohwada C, Takeuchi M, Takeda Y, Mimura N, Iseki T, Wu S, Arai M, Imazeki F, Saito K, Shirasawa H, Yokosuka O.
  • Journal Title: Int J Mol Sci. Volume: 15 Pages: 21455-21467
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hepatitis C Virus Nonstructural Protein 5A Inhibits Thapsigargin-Induced Apoptosis (2014)
  • Author(s): Xia Jiang, Tatsuo Kanda, Shuang Wu, Shingo Nakamoto, Takaji Wakita, Hiroshi Shirasawa, Osamu Yokosuka.
  • Journal Title: PLoS ONE Volume: 9 Issue: 11 Pages: e113499-e113499
  • DOI: 10.1371/journal.pone.0113499
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppression of La Antigen Exerts Potential Antiviral Effects against Hepatitis A Virus. (2014)
  • Author(s): Jiang X, Kanda T, Wu S, Nakamoto S, Saito K, Shirasawa H, Kiyohara T, Ishii K, Wakita T, Okamoto H, Yokosuka O.
  • Journal Title: PLoS One. Volume: 9 Issue: 7 Pages: e101993-e101993
  • DOI: 10.1371/journal.pone.0101993
  • Peer Reviewed / Open Access
• [Journal Article] , Hepatitis C virus NS5A inhibitors and drug resistance mutations. (2014)
  • Author(s): Nakamoto S, Kanda T, Wu S, Shirasawa H, Yokosuka O.
  • Journal Title: World J Gastroenterol Volume: 20 Pages: 2902-2912
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ベンゾイミダゾール誘導体 C299-1 による癌細胞傷害機序の解析 (2016)
  • Author(s): 大野 吉史、蟻 瑞栄、陳 偉巍、田 錚、郭 書翰、李 斉森、馬 雪、菅波 晃子、田村 裕、松本 明郎、松本 祥治、齋藤 謙悟、白澤 浩
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-06
• [Presentation] 新規化合物 CCL-113 は M 期とエンドサイクルを誘導する (2016)
  • Author(s): 坪坂 歩、蟻 瑞栄、大野 吉史、陳 偉巍、田 錚、郭 書翰、李 斉森、馬 雪、菅波 晃子、齋藤 謙悟、田村 裕、白澤 浩
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-06
• [Presentation] Alteration of cell cycle progression by Sindbis virus infection (2016)
  • Author(s): Yoshifumi Ohno, Yi Ruirong, Chen Weiwei, Tian Zheng, Guo Shuhan, Qisen Li, Ma Xue, Akiko Suganami, Kengo Saito, Yutaka Tamura, Naohisa Isegawa, Hiroshi Shirasawa
  • Organizer: The 64th annual meeting of the Japanese society for virology
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
• [Presentation] Screening and identification of compounds with antiviral activity against human respiratory syncytial virus. (2015)
  • Author(s): Yoshifumi Ohno, Yi Ruirong, Chen Weiwei, Tian Zheng, Guo Shuhan, Ma Xue, Akiko Suganami, Kengo Saito, Yutaka Tamura, Hiroshi Shirasawa
  • Organizer: The 63rd annual meeting of the Japansese society for virology
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2015-11-22
• [Presentation] 悪性黒色腫治療へのLP-iDOPEの適用 (2015)
  • Author(s): 菅波 晃子、篠田 健太、鈴木 茜、齋藤 謙悟、岡本 芳晴、本橋 新一郎、中山 俊憲、白澤 浩、田村 裕
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 腫瘍溶解ウイルスSindbis virusは癌細胞をS期に誘導する (2015)
  • Author(s): 大野 吉史、蟻 瑞栄、陳 偉巍、田 錚、郭 書翰、馬 雪、菅波 晃子、齋藤 謙悟、伊勢川 直久、田村 裕、白澤 浩
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08