The development of the novel targeted adenovirus vectors

• Project/Area Number: 22390030
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Osaka University
• Principal Investigator: MIZUGUCHI Hiroyuki 大阪大学, 大学院・薬学研究科, 教授 (50311387)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2010: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: アデノウイルスベクター / ターゲティング / 一本鎖抗体 / 遺伝子治療 / ファージ表面提示法 / ポリエチレングリコール / ファージライブラリ / 遺伝子発現 / 抗体 / 癌治療

Research Abstract

To accomplish successful gene therapy,it is necessary to deliver the gene safely into targeted tissues and cells with the stable gene expression. We developed the novel targeted adenovirus (Ad) vectors using the strategies of the chemical or genetic engineering modification of Ad capsid protein and the insertion of the novel targeting molecules into Ad vector

Research Products

• [Journal Article] A targeted adenovirus vector displaying a human fibronectin type III domain-based monobody in a fiber protein. (2013)
  • Author(s): Matsui H, Sakurai F, Katayama K, Abe Y, Machitani M, Kurachi S, Tachibana M, Mizuguchi H.
  • Journal Title: Biomaterials Volume: 34 Pages: 4191-201
• [Journal Article] A targeted adenovirus vector displaying a human fibronectin type III domain-based monobody in a fiber protein (2013)
  • Author(s): Matsui H, et al.
  • Journal Title: Biomaterials Volume: 34 Issue: 16 Pages: 4191-4201
  • DOI: 10.1016/j.biomaterials.2013.02.046
  • Peer Reviewed
• [Journal Article] A hexon-specific PEGylated adenovirus vector utilizing blood coagulation factor X (2012)
  • Author(s): Matsui H, Sakurai F, Katayama K, Yamaguchi T, Okamoto S, Takahira K, Tachibana M, Nakagawa S, Mizuguchi H.
  • Journal Title: Biomaterials. Volume: 33 Pages: 3743-55
• [Journal Article] Further reduction in adenovirus vector-mediated liver transduction without largely affecting transgene expression in target organ by exploiting microRNA-mediated regulation and the Cre-loxP recombination system (2012)
  • Author(s): Bennett D, Sakurai F, Shimizu K, Matsui H, Tomita K, Suzuki T, Katayama K, Kawabata K, Mizuguchi H.
  • Journal Title: Mol. Pharmaceutics Volume: 9 Pages: 3452-3463
• [Journal Article] Intramuscular DNA immunization with in vivo electroporation induces antigen- specific cellular and humoral immune responses in both systemic and gut-mucosal compartments. (2012)
  • Author(s): Shoji M, Katayama K, Tachibana M, Tomita K, Sakurai F, Kawabata K, Mizuguchi H
  • Journal Title: Vaccine. Volume: 30 Pages: 7278-85
• [Journal Article] Type-I IFN signaling is required for the induction of antigen-specific CD8(+) T cell responses by adenovirus vector vaccine in the gut-mucosa (2012)
  • Author(s): Shoji M, Tachibana M, Katayama K, Tomita K, Tsuzuki S, Sakurai F, Kawabata K, Ishii KJ, Akira S, Mizuguchi H.
  • Journal Title: Biochem Biophys Res Commun Volume: 425 Pages: 89-93
• [Journal Article] Correlation between adenovirus-neutralizing antibody titer and adenovirus vector- mediated transduction efficiency following intratumoral injection (2012)
  • Author(s): Tomita K., Sakurai F., Tachibana M., Mizuguchi H
  • Journal Title: Anticancer Res Volume: 32 Pages: 1145-1152
• [Journal Article] Efficient antitumor effects of carrier cells loaded with a fiber-substituted conditionally replicating adenovirus on CAR-negative tumor cells. (2012)
  • Author(s): Iguchi K., Sakurai F., Tomita K., Katayama K., Yamaguchi T., Tagawa M., Kawabata M., Shirakawa T., Mizuguchi H.
  • Journal Title: Cancer Gene Ther Volume: 19 Pages: 118-125
• [Journal Article] Further Reduction in Adenovirus Vector-Mediated Liver Transduction without Largely Affecting Transgene Expression in Target organ by Exploiting MicroRNA-Mediated Regulation and the Cre-1oxP Recombination System. (2012)
  • Author(s): Bennet D, et al.
  • Journal Title: Molecular Pharmaceutics Volume: 9 Issue: 12 Pages: 3452-3463
  • DOI: 10.1021/mp300248u
  • Peer Reviewed
• [Journal Article] Intramuscular DNA immunization with in vivo electroporation induces antigen-specific cellular and humoral immune responses in both systemic and gut-mucosal compartments (2012)
  • Author(s): Shoji M.
  • Journal Title: Vaccine Volume: 30 Issue: 50 Pages: 7278-7285
  • DOI: 10.1016/j.vaccine.2012.09.046
  • Peer Reviewed
• [Journal Article] Type-I IFN signaling is required for the induction of antigen-specific CD8＋ T cell responses by adenovirus vector vaccine in the gut-mucosa (2012)
  • Author(s): Shoji M.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 425 Issue: 1 Pages: 89-93
  • DOI: 10.1016/j.bbrc.2012.07.056
  • Peer Reviewed
• [Journal Article] Correlation between adenovirus-neutralizing antibody titer and adenovirus vector-mediated transduction efficiency following intratumoral injection (2012)
  • Author(s): Tomita K.
  • Journal Title: Anticancer Res. Volume: 32 Pages: 1145-1152
  • Peer Reviewed
• [Journal Article] A hexon-specific PEGylated adenovirus vector utilizing blood coagulation factor X (2012)
  • Author(s): Matsui H, et al
  • Journal Title: Biomaterials Volume: 33 Issue: 14 Pages: 3743-3755
  • DOI: 10.1016/j.biomaterials.2012.02.011
  • Peer Reviewed
• [Journal Article] Efficient antitumor effects of carrier cells loaded with a fiber-substituted conditionally replicating adenovirus on CAR-negative tumor cells (2012)
  • Author(s): Iguchi K.
  • Journal Title: Cancer Gene Ther. Volume: 19 Issue: 2 Pages: 118-125
  • DOI: 10.1038/cgt.2011.74
  • Peer Reviewed
• [Journal Article] Quantitative analysis of the leaky expression of adenovirus genes in cells transduced with a replication-incompetent adenovirus vector (2012)
  • Author(s): Shimizu K, et al
  • Journal Title: Mol.Pharmaceutics Volume: 8 Issue: 4 Pages: 1430-1435
  • DOI: 10.1021/mp200121z
  • Peer Reviewed
• [Journal Article] Enhanced transduction efficiency of fiber-substituted adenovirus vectors by the incorporation of RGD peptides in two distinct regions of the adenovirus serotype 35 fiber knob. (2011)
  • Author(s): Matsui H, Sakurai F, Katayama K, Kurachi S, Tashiro K, Sugio K, Kawabata K, Mizuguchi H
  • Journal Title: Virus Research Volume: 155 Pages: 48-54
• [Journal Article] An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors (2011)
  • Author(s): Motegi Y, et al
  • Journal Title: J Control Release Volume: 153 Issue: 2 Pages: 149-153
  • DOI: 10.1016/j.jconrel.2011.04.009
  • Peer Reviewed
• [Journal Article] Development of an adenovirus vector lacking the expression of virus-associated RNAs (2011)
  • Author(s): Machitani M, et al
  • Journal Title: J Control Release Volume: 154 Issue: 3 Pages: 285-289
  • DOI: 10.1016/j.jconrel.2011.06.020
  • Peer Reviewed
• [Journal Article] Hexon-specific PEGylated adenovirus vectors utilizing avidin-biotin interaction (2011)
  • Author(s): Suzuki-Kouyama E, et al
  • Journal Title: Biomaterials Volume: 32 Issue: 6 Pages: 1724-1730
  • DOI: 10.1016/j.biomaterials.2010.10.060
  • Peer Reviewed
• [Journal Article] Adenovirus vector-derived VA-RNA-mediated innate immune responses (2011)
  • Author(s): Machitani M, et al
  • Journal Title: Pharmaceutics Volume: 3 Issue: 3 Pages: 338-353
  • DOI: 10.3390/pharmaceutics3030338
  • Peer Reviewed
• [Journal Article] Development of improved adenovirus vectors and transduction into neural cells (2011)
  • Author(s): 松井勇人, et al
  • Journal Title: Folia Pharmacologica Japonica Volume: 137 Issue: 2 Pages: 70-74
  • DOI: 10.1254/fpj.137.70
  • NAID: 10029417046
  • ISSN: 0015-5691, 1347-8397
• [Journal Article] ウイルスベクターと遺伝子治療 (2011)
  • Author(s): 水口裕之、櫻井文教
  • Journal Title: 化学療法の領域 Volume: 27 Pages: 867-873
• [Journal Article] Hexon-specific PEGylated adenovirus vectors utilizing avidin-biotin interaction. (2011)
  • Author(s): Suzuki-Kouyama E., et al.
  • Journal Title: Biomaterials Volume: 32 Pages: 1724-1730
  • Peer Reviewed
• [Journal Article] Enhanced transduction efficiency of fiber-substituted adenovirus vectors by the incorporation of RGD peptides in two distinct regions of the adenovirus serotype 35 fiber knob. (2011)
  • Author(s): Matsui H., et al.
  • Journal Title: Virus Res. Volume: 155 Pages: 48-54
  • Peer Reviewed
• [Journal Article] Optimized PEGylated adenovirus vector reduces the anti-vector humoralimmune response against adenovirus and induces a therapeutic effect against metastatic lung cancer. (2010)
  • Author(s): Eto Y., et al.
  • Journal Title: Biol Pharm Bull. Volume: 33 Pages: 1540-1544
  • Peer Reviewed
• [Journal Article] EpCAM- and EGFR- targeted selective gene therapy for biliary cancers using Z33-fiber modified adenovirus.
  • Author(s): Kawashima R., et al.
  • Journal Title: Int.J.Cancer Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] ウイルスベクターと遺伝子治療
  • Author(s): 水口裕之、櫻井文教
  • Journal Title: 化学療法の領域 Volume: (印刷中)
• [Presentation] 組織特異的ターゲティングを目指した Monobody 提示型 Ad ベクターの開発 (2013)
  • Author(s): 松井勇人、櫻井文教、形山和史、阿部康弘、町谷充洋、倉知慎之輔、立花雅史、水口裕之
  • Organizer: 日本薬学会 第133 年会
  • Place of Presentation: 横浜
• [Presentation] 組織特異的ターゲティングを目指したMonobody提示型Adベクターの開発 (2013)
  • Author(s): 松井勇人
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] アデノウイルスベクター局所投与による遺伝子発現への抗アデノウイルス抗体の影響 (2012)
  • Author(s): 冨田恭子、櫻井文教、庄司正樹、立花雅史、水口裕之
  • Organizer: 日本薬学会第132回年会
  • Place of Presentation: 北海道
• [Presentation] 血液凝固因子(FX) を利用した新規 PEG 化アデノウイルスベクターの開発 (2012)
  • Author(s): 松井勇人、櫻井文教、形山和史、山口朋子、岡本小百合、高比良幸大、立花雅史、水口裕之
  • Organizer: 第28回 日本DDS学会
  • Place of Presentation: 札幌
• [Presentation] IN VITRO TRANSDUCTION PROPERTIES OF A NOVEL TARGETED ADENOVIRUS VECTOR DISPLAYING MONOBODY BINDING TO VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2 IN A FIBER PROTEIN. (2012)
  • Author(s): Matsui H, Sakurai F, Tachibana M, Kurachi S, Katayama K, Mizuguchi H
  • Organizer: 第18回 日本遺伝子治療学会
  • Place of Presentation: 熊本
• [Presentation] Development of a Novel targeted Adenovirus Vector Displaying Monobody Binding to Anti-Vascular Endothelial Growth Factor Receptor 2 in a Fiber Protein. (2012)
  • Author(s): Matsui H, Sakurai F, Tachibana M, Kurachi S, Katayama K, Mizuguchi H
  • Organizer: American Society of Gene & Cell Therapy 15th Annual Meeting
  • Place of Presentation: アメリカ (フィラデルフィア)
• [Presentation] EFFECT OF ADENOVIRUS-NEUTRALIZING ANTIBODY ON ADENOVIRUS VECTOR-MEDIATED TRANSGENE EXPRESSION FOLLOWING INTRATUMORAL INJECTION (2012)
  • Author(s): Tomita K, Sakurai F, Tachibana M, Mizuguchi H
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
• [Presentation] In vitro transduction properties of a novel targeted adenovirus vector displaying monobody binding to vascular endothelial growth factor receptor 2 in a fiber protein (2012)
  • Author(s): Matsui H.
  • Organizer: 第18回日本遺伝子治療学会学術集会
  • Place of Presentation: Hotel Kumamoto Terrsa
• [Presentation] Development of a Novel Targeted Adenovirus Vector Displaying Monobody Binding to Anti-Vascular Endothelial Growth Factor Receptor 2 in a Fiber Protein (2012)
  • Author(s): Matsui H.
  • Organizer: ASGCT 15th Annual Meeting
  • Place of Presentation: Pennsylvania Convention Center, USA
• [Presentation] アデノウイルスベクターに対する免疫応答が繰り返し投与による遺伝子導入に与える影響に関する検討 (2012)
  • Author(s): 森大輔, et al
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] アデノウイルスベクターによるオートファジーの誘導と遺伝子発現への影響 (2011)
  • Author(s): 島岡恵里, et al
  • Organizer: 第61回日本薬学会近畿支部総会・大会
  • Place of Presentation: 神戸
  • Year and Date: 2011-10-22
• [Presentation] In Vitro Transduction Properties of Fiber-substituted Adenovirus Vectors Containing Foreign Peptides in the Adenovirus Serotype 35 Fiber Knob. (2011)
  • Author(s): Matsui H, Sakurai F, Katayama K, Kurachi S, Tashiro K, Sugio K, Kawabata K, Mizuguchi H
  • Organizer: The 6thSeoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
  • Place of Presentation: 韓国(ソウル)
• [Presentation] Fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob (2011)
  • Author(s): Matsui H, et al
  • Organizer: The 6th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
  • Place of Presentation: 韓国(ソウル)
• [Presentation] Development of adenovirus vector lacking the expression of virus-associated RNAs (2011)
  • Author(s): Machitani M, et al
  • Organizer: The 6th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
  • Place of Presentation: 韓国(ソウル)
• [Presentation] Development of a virus-associated RNA-deleted adenovirus vector (2011)
  • Author(s): Machitani M, et al
  • Organizer: American Society of Gene & Cell Therapy, 14th Annual Meeting 2011
  • Place of Presentation: アメリカ(シアトル)
• [Presentation] アデノウイルス由来小分子RNA(VA-RNA)の機能解析に向けた新規ベクターの開発 (2011)
  • Author(s): 町谷充洋, et al
  • Organizer: 第21回アンチセンスシンポジウム・第11回遺伝子・デリバリー研究会シンポジウム合同シンポジウム
  • Place of Presentation: 大阪
• [Presentation] Development of adenovirus vector lacking virus-associated RNA expression (2011)
  • Author(s): Mitsuhiro Machitani, et al
  • Organizer: 第17回日本遺伝子治療学会総会
  • Place of Presentation: 福岡
• [Presentation] 増殖型アデノウイルスベクターより非特異的に発現するウイルス遺伝子の定量的発現解析 (2011)
  • Author(s): 清水かほり, 他
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] ENHANCED TRANSDUCTION EFFICIENCIES OF FIBER-SUBSTITUTED ADENOVIRUS VECTORS BY INCORPORATION OF RGD PEPTIDE IN TWO DISTINCT REGIONS OF ADENOVIRUS SEROTYPE 35 FIBER KNOB (2010)
  • Author(s): Matsui H, Sakurai F, Katayama K, Kurachi S, Tashiro K, Sugio K, Kawabata K, Mizuguchi H
  • Organizer: 第16回日本遺伝子治療学会
  • Place of Presentation: 栃木
• [Presentation] ラクダ抗体重鎖可変ドメインによる細胞特異的ターゲティングを目指した新規 Ad ベクターの開発 (2010)
  • Author(s): 松井勇人、形山和史、櫻井文教、倉知慎之輔、田代克久、川端健二、萩原義久、水口裕之
  • Organizer: 第26回日本 DDS 学会
  • Place of Presentation: 大阪
• [Presentation] 特異的標的化を可能とするアデノウイルスベクターの開発 (2010)
  • Author(s): 水口裕之
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸(招待講演)
• [Presentation] 次世代アデノウイルスベクターの開発と生命科学研究への応用 (2010)
  • Author(s): 水口裕之
  • Organizer: 第26回日本DDS学会
  • Place of Presentation: 大阪(招待講演)
• [Presentation] ENHANCED TRANSDUCTION EFFICIENCIES OF FIBER-SUBSTITUTED ADENOVIRUS VECTORS BY INCORPORATION OF RGD PEPTIDE IN TWO DISTINCT REGIONS OF ADENOVIRUS SEROTYPE 35 FIBER KNOB. (2010)
  • Author(s): Hayato Matsui, 他
  • Organizer: 第16回日本遺伝子治療学会
  • Place of Presentation: 宇都宮
• [Presentation] ラクダ抗体重鎖可変ドメインによる細胞特異的ターゲティングを目指した新規アデノウイルスベクターの開発 (2010)
  • Author(s): 松井勇人, 他
  • Organizer: 第26回日本DDS学会
  • Place of Presentation: 大阪
• [Remarks]
  • URL: https://sites.google.com/site/bunshiseibutugaku/
• [Remarks] 大阪大学大学院薬学研究科 分子生物学分野HP
  • URL: https://sites.google.com/site/bunshiseibutugaku/
• [Remarks]
  • URL: https://sites.google.com/site/bunshiseibutugaku/
• [Remarks]
  • URL: https://sites.google.com/site/bunshiseibutugaku/
• [Remarks]
  • URL: http://www.nibio.go.jp/Proj3HP/pub2011.html