Systemic siRNA delivery to prevent interferon-response in animals

• Project/Area Number: 21590305
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: TAKEI Yoshifumi 名古屋大学, 大学院・医学系研究科, 准教授 (70362233)
• Co-Investigator(Kenkyū-buntansha): KADOMATSU Kenji 名古屋大学, 大学院・医学系研究科, 教授 (80204519)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: RNA干渉 / siRNA / インターフェロン応答 / 薬物送達 / 自然免疫 / 塩基配列 / 末梢血単核球細胞 / 治療

Research Abstract

RNA interference is an endogenous gene-silencing method that involves double-stranded short RNA(siRNA)-mediated sequence-specific mRNA degradation. Here, we showed intravenously administered siRNA/atelocollagen complex did not induce immunostimulatory adverse effects(interferon-response) in mice. We also found the complex did not entered into peripheral blood mononuclear cells as a reason of the immunostimulatory-null effect of the complex. Atelocollagen is an excellent and promising delivery vehicle, and it has the useful advantage of evading detection by the" radar" of innate immunity.

Research Products

• [Journal Article] Amino-modified and lipid-conjugated dicer-substrate siRNA enhances RNAi efficacy (2012)
  • Author(s): Kubo T, Takei Y, Mihara K, Yanagihara K, Seyama T.
  • Journal Title: Bioconjugate Chem Volume: 23 Pages: 164-173
  • Peer Reviewed
• [Journal Article] Over expression of BMI-1 correlates with drug resistance in B-cell lymphoma cells through the stabilization of survivin expression (2012)
  • Author(s): Bhattacharyya J, Mihara K, Ohtsubo M, Yasunaga S, Takei Y, Yanagihara K, Sakai A, Hoshi M, Takihara Y, Kimura A.
  • Journal Title: Cancer Sci Volume: 103 Pages: 34-41
  • Peer Reviewed
• [Journal Article] Atelocollagen-mediated systemic delivery prevents immunostimulatory adverse effects of siRNA in mammals (2012)
  • Author(s): Inaba S, Nagahara S, Makita N, Tarumi Y, Ishimoto T, Matsuo S, Kadomatsu K, Takei Y.
  • Journal Title: Mol Ther Volume: 20 Pages: 356-366
  • Peer Reviewed
• [Journal Article] T-cell immunotherapy with a chimeric receptor against CD38 is effective in eliminating myeloma cells (2012)
  • Author(s): Mihara K, Bhattacharyya J, Kitanaka A, Yanagihara K, Kubo T, Takei Y, Asaoku H, Takihara Y, Kimura A.
  • Journal Title: Leukemia Volume: 26 Pages: 365-367
  • Peer Reviewed
• [Journal Article] Atelocollagen-mediated systemic delivery prevents immunostimulatory adverse effects of siRNA in mammals (2012)
  • Author(s): Inaba S, Nagahara S, Makita N, Tarumi Y, Ishimoto T, Matsuo S, Kadomatsu K, Takei Y
  • Journal Title: Molecular Therapy Volume: 20 Issue: 2 Pages: 356-366
  • DOI: 10.1038/mt.2011.221
  • Peer Reviewed
• [Journal Article] Palmitic acid-conjugated 21-nt siRNA enhances gene-silencing activity (2011)
  • Author(s): Kubo T, Yanagihara K, Takei Y, Mihara K, Morita Y, Seyama T.
  • Journal Title: Mol Pharm Volume: 8 Pages: 2193-2203
  • Peer Reviewed
• [Journal Article] The premature ligand-receptor interaction during biosynthesis limits the production of growth factor midkine and its receptor LDL receptor-related protein 1(LRP1) (2011)
  • Author(s): Sakamoto K, Bu G, Chen S, Takei Y, Hibi K, Kodera Y, MaCormick LM, Nakao A, Noda M, Muramatsu T, Kadomatsu K.
  • Journal Title: J Biol Chem Volume: 286 Pages: 8405-8413
  • Peer Reviewed
• [Journal Article] The metastasis-associated microRNA miR-516a-3p is a novel therapeutic target for inhibiting peritoneal dissemination of human scirrhous gastric cancer (2011)
  • Author(s): Takei Y, Takigahira M, Mihara K, Tarumi Y, Yanagihara K.
  • Journal Title: Cancer Res Volume: 71 Pages: 1442-1453
  • Peer Reviewed
• [Journal Article] Peritoneal macrophage infiltration is correlated with baseline peritoneal solute transport rate in peritoneal dialysis patients (2011)
  • Author(s): Sawai A, Ito Y, Mizuno M, Suzuki Y, Toda S, Ito I, Hattori R, Matsukawa Y, Gotoh M, Takei Y, Yuzawa Y, Matsuo S.
  • Journal Title: Nephrol Dial Transplant Volume: 26 Pages: 2322-2332
  • Peer Reviewed
• [Journal Article] Palmitic acid-conjugated 21-nt siRNA enhances gene-silencing activity (2011)
  • Author(s): Kubo T, Yanagihara K, Takei Y, Mihara K, Morita Y, Seyama T
  • Journal Title: Molecular Pharmaceutics Volume: 8 Issue: 6 Pages: 2193-2203
  • DOI: 10.1021/mp200250f
  • Peer Reviewed
• [Journal Article] The metastasis-associated microRNA miR-516a-3p is a novel therapeutic target for inhibiting peritoneal dissemination of human scirrhous gastric cancer (2011)
  • Author(s): Takei Y, Takigahira M, Mihara K, Tarumi Y, Yanagihara K
  • Journal Title: Cancer Research Volume: 71 Pages: 1442-1453
  • Peer Reviewed
• [Journal Article] Peritoneal macrophage infiltration is correlated with baseline peritoneal solute transport rate in peritoneal dialysis patients (2011)
  • Author(s): Sawai A, Ito Y, Mizuno M, Suzuki Y, Toda S, Ito I, Hattori R, Matsukawa Y, Gotoh M, Takei Y, Yuzawa Y, Matsuo S
  • Journal Title: Nephrology Dialysis Transplantation Volume: 26 Pages: 2322-2332
  • Peer Reviewed
• [Journal Article] The premature ligand-receptor interaction during biosynthesis limits the production of growth factor midkine and its receptor LDL receptor-related protein 1 (LRP1) (2011)
  • Author(s): Sakamoto K, Bu G, Chen S, Takei Y, Hibi K, Kodera Y, MaCormick LM, Nakao A, Noda M, Muramatsu T, Kadomatsu K
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 8405-8413
  • Peer Reviewed
• [Journal Article] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cellnon-Hodgkin's lymphoma (2010)
  • Author(s): Mihara K, Yanagihara K, Takigahira M, Kitanaka A, Imai C, Bhattacharyya J, Kubo T, Takei Y, Yasunaga S, Takihara Y, Kimura A
  • Journal Title: Br J Haematol Volume: 151 Pages: 37-46
  • Peer Reviewed
• [Journal Article] EWS/Fli-1 chimeric fusion gene up-regulates vascular endothelial growth factor-A (2010)
  • Author(s): Nagano A, Ohno T, Shimizu K, Hara A, Yamamoto T, Kawai G, Saitou M, Takigami I, Matsuhashi A, Yamada K, Takei Y.
  • Journal Title: Int J Cancer Volume: 126 Pages: 2790-2798
  • Peer Reviewed
• [Journal Article] EWS/Fli-1 chimeric fusion gene up-regulates vascular endothelial growth factor-A (2010)
  • Author(s): Nagano A, Ohno T, Shimizu K, Hara A, Yamamoto T, Kawai G, Saitou M, Takigami I, Matsuhashi A, Yamada K, Takei Y
  • Journal Title: International Journal of Cancer Volume: 126 Pages: 2790-2798
  • Peer Reviewed
• [Journal Article] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin's lymphoma (2010)
  • Author(s): Mihara K, Yanagihara K, Takigahira M, Kitanaka A, Imai C, Bhattacharyya J, Kubo T, Takei Y, Takihara Y, Kimura A
  • Journal Title: British Journal of Haematology Volume: 151 Pages: 37-46
  • Peer Reviewed
• [Journal Article] EWS/Fli-1 chimeric fusion gene up-regulates vascular endothelial growth factor-A. (2010)
  • Author(s): Nagano A, Ohno T, Shimizu K, Hara A, Yamamoto T, Kawai G, Saitou M, Takigami I, Matsuhashi A, Yamada K, Takei Y.
  • Journal Title: International Journal of Cancer (in press)
  • Peer Reviewed
• [Journal Article] Lymphatic vessels develop in tubulo-interstitial fibrosis (2009)
  • Author(s): Sakamoto I, Ito Y, Mizuno M, Suzuki Y, Sawai A, Tanaka A, Maruyama S, Takei Y, Yuzawa Y, Matsuo S.
  • Journal Title: Kidney Int Volume: 75 Pages: 828-838
  • Peer Reviewed
• [Journal Article] Systemic delivery of siRNA specific to tumor mediated by atelocollagen : Combined therapy using siRNA targeting Bcl-xL and cisplatin against prostate cancer (2009)
  • Author(s): Mu P, Nagahara S, Makita N, Tarumi Y, Kadomatsu, K, Takei Y.
  • Journal Title: Int J Cancer Volume: 125 Pages: 2978-2990
  • Peer Reviewed
• [Journal Article] Systemic delivery of siRNA specific to tumor mediated by atelocollagen : Combined therapy using siRNA targeting Bcl-xL and cisplatin against prostate cancer. (2009)
  • Author(s): Mu P, Nagahara S, Makita N, Tarumi Y, Kadomatsu, K, Takei Y.
  • Journal Title: International Journal of Cancer 125 Pages: 2978-2990
  • Peer Reviewed
• [Journal Article] Lymphatic vessels develop in tubulo-interstitial fibrosis. (2009)
  • Author(s): Sakamoto I, Ito Y, Mizuno M, Suzuki Y, Sawai A, Tanaka A, Maruyama S, Takei Y, Yuzawa Y, Matsuo S.
  • Journal Title: Kidney International 75 Pages: 828-838
  • Peer Reviewed
• [Journal Article] TGF-SS induces VEGF-C expression leading to lymph angiogenesis in rat unilateral ureteral obstruction
  • Author(s): Suzuki Y, Ito Y, Mizuno M, Kinashi H, Sawai A, Noda Y, Mizuno T, Shimizu H, Fujita Y, Matsui K, Maruyama S, Imai E, Matsuo S, Takei Y.
  • Journal Title: Kidney Int
  • Peer Reviewed
• [Presentation] Lymphangiogenesis develops during peritoneal fibrosis in peritoneal dialys is patients and rat peritonitis model (2011)
  • Author(s): Kinashi H, Ito Y, Mizuno M, Suzuki Y, Nagura F, Sato W, Tsuboi N, Maruyama S, Imai E, Takei Y, Matsuo S
  • Organizer: American Society of Nephrology, Renal Week 2011
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 2011-11-10
• [Presentation] Lymphangiogenesis develops during peritoneal fibrosis in peritoneal dialysis patients and rat peritonitis model (2011)
  • Author(s): Kinashi H, Ito Y, Mizuno M, Suzuki Y, Nagura F, Sato W, Tsuboi N, Maruyama S, Imai E, Takei Y, Matsuo S.
  • Organizer: Renal Week 2011
  • Place of Presentation: Renal Week 2011
  • Year and Date: 2011-10-08
• [Presentation] miR-302ファミリーの導入によってHEK293細胞からリプログラミングしたmirPS細胞における網羅的遺伝子発現解析 (2011)
  • Author(s): 小出直史、武井佳史
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2011-09-23
• [Presentation] miR-302ファミリーの導入によってHEK293細胞からリプログラミングしたmirPS細胞における網羅的遺伝子発現解析 (2011)
  • Author(s): 小出直史、武井佳史
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2011-09-23
• [Presentation] 脂肪酸コンジュゲート2本鎖RNAはRNA干渉効果を向上するアンチセンス・遺伝子・デリバリーシンポジウム2011 (2011)
  • Author(s): 久保貴紀、柳原五吉、武井佳史、瀬山敏雄
  • 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: 吹田市
  • Year and Date: 2011-09-01
• [Presentation] 脂肪酸コンジュゲート2本鎖RNAはRNA干渉効果を向上する (2011)
  • Author(s): 久保貴紀、柳原五吉、武井佳史、瀬山敏雄
  • Organizer: アンチセンス・遺伝子・デリバリーシンポジウム2011(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: 大阪大学コンベンションセンター(吹田市)
  • Year and Date: 2011-09-01
• [Presentation] Antimetastatic the rapy for human scirrhous gastric cancers tore press their peritoneal disseminationvia microRNA-based medicine (2011)
  • Author(s): Takei Y.
  • Organizer: New Trendsin Basic and Clinical Cancer Researchfor Innovative Therapy
  • Place of Presentation: Nagoya, JAPAN
• [Presentation] Systemic delivery of siRNAspecific to tumor mediated byatelocollagen : Combined the rapy usingsiRNA targeting Bcl-xL and cisplatinagainst prostate cancer (2010)
  • Author(s): Takei Y.
  • Organizer: The International Chemical Congress of Pacific Basin Societies.
  • Place of Presentation: Honolulu, Hawai, USA
  • Year and Date: 2010-12-16
• [Presentation] Systemic delivery of siRNA specific to tumor mediated by atelocollagen : Combined therapy using siRNA targeting Bcl-xL and cisplatin against prostate cancer (2010)
  • Author(s): Takei Y.
  • Organizer: The International Chemical Congress of Pacific Basin Societies (American Chemical Society)
  • Place of Presentation: Honolulu, Hawai, USA
  • Year and Date: 2010-12-16
• [Presentation] Peritoneal macrophage infiltration is correlated with baseline peritoneal solute transport rate in peritoneal dialysis patients. American Society of Nephrology (2010)
  • Author(s): Sawai A, Ito Y, Mizuno, M, Suzuki Y, Toda S, Ito I, Sato W, Tsuboi N, Maruyama S, Imai E, Takei Y, Yuzawa, Y, Matsuo S.
  • Organizer: Renal Week 2010
  • Place of Presentation: Colorado Convention Center, Denver, CO, USA
  • Year and Date: 2010-11-16
• [Presentation] Lymphangiogenesisdevelops during tubulo-interstitialfibrosis via the TGFb-VEGF-C pathwayin rat unilateral ureteral obstruction. American Society of Nephrology (2010)
  • Author(s): Suzuki Y, Ito Y, Mizuno M, Sawai A, Kinashi H, Sato W, Maruyama S, Imai E, Takei Y, Matsuo S.
  • Organizer: Renal Week 2010
  • Place of Presentation: Colorado Convention Center, Denver, CO, USA
  • Year and Date: 2010-11-16
• [Presentation] microRNAの特異的制御によるヒトスキルス胃癌の腹膜播種性転移抑止 (2010)
  • Author(s): 武井佳史
  • Organizer: 第697回千葉県がんセンター研究局集談会
  • Place of Presentation: 千葉県がんセンター(千葉市)
  • Year and Date: 2010-10-06
• [Presentation] MicroRNA-516a-3pはヒトスキルス胃癌の腹膜播種性転移抑止の標的となりうる新規metastamirである (2010)
  • Author(s): 武井佳史、柳原五吉
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-24
• [Presentation] MicroRNA-516a-3pはヒトスキルス胃癌の腹膜播種性転移抑止の標的となりうる新規metastamirである (2010)
  • Author(s): 武井佳史、柳原五吉
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-09-24
• [Presentation] 血管内皮増殖因子の発現を抑制するsiRNAの作成と腫瘍への電気的導入法について (2010)
  • Author(s): 武井佳史
  • Organizer: 第9回バイオテクノロジー国際会議・バイオアカデミックフォーラム
  • Place of Presentation: 東京ビッグサイト(東京都)
  • Year and Date: 2010-07-01
• [Presentation] Systemic delivery of siRNA specific to tumor mediated by atelocollagen : Combined therapy using siRNA targetingBcl-xL and cisplatin against prostate cancer (2010)
  • Author(s): ムー・ピン、門松健治、武井佳史
  • Organizer: 第74回日本生化学会中部支部例会・シンポジウム
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-05-29
• [Presentation] Lymph angiogenesis develop during tubulointer stitial fibrosis in ratunilateral ureteral obstruction viaTGF-VEGF-C pathway (2010)
  • Author(s): Suzuki Y, Ito Y, Mizuno M, Sawai A, Kinashi H, Sato W, Maruyama S, Takei Y, Imai E, Yuzawa Y, Matsuo S.
  • Organizer: Emerging Culprits in Pathogenesis and Advances in Therapy
  • Place of Presentation: Kyoto
  • Year and Date: 2010-04-15
• [Presentation] 癌腹膜播種性転移を制御するmiRNAの同定とその転移抑止の治療戦略 (2010)
  • Author(s): 武井佳史
  • Organizer: 第14回神経芽腫研究会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-03-06
• [Presentation] Systemic delivery of siRNAspecific to tumor mediated byatelocollagen : Combined therapy usingsiRNA targeting Bcl-xL and cisplatinagainst prostate cancer (2010)
  • Author(s): Takei Y.
  • Organizer: 8th JointConference of the American Associationfor Cancer Research and the Japanese Cancer Association
  • Place of Presentation: Hilton WaikoloaVillage, Waikoloa, Hawaii, USA
  • Year and Date: 2010-02-05
• [Presentation] アテロコラーゲンによる腫瘍特異的なsiRNA全身デリバリー法 (2009)
  • Author(s): 武井佳史
  • Organizer: 第82回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸市
  • Year and Date: 2009-10-24
• [Presentation] アテロコラーゲンによる腫瘍特異的なsiRNA全身デリバリー法 (2009)
  • Author(s): 武井佳史
  • Organizer: 第82回 日本生化学会大会 シンポジウム
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 2009-10-24
• [Presentation] MicroRNA-516a-3pはヒトスキルス胃癌の腹膜播種性転移に関与する (2009)
  • Author(s): 武井佳史、柳原五吉
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-02
• [Book] Midkine and chemoresistance in cancers. Midkine : From Embryogenesis to Pathogenesis and Medication (2012)
  • Author(s): Takei Y, Kadomatsu K
  • Publisher: Springer
• [Book] Midkine and chemoresistance in cancers. Midkine : From Embryogenesis to Pathogenesis and Medication (2012)
  • Author(s): Takei Y, Kadomatsu K
  • Publisher: Springer社(印刷中)
• [Book] Patients : Plasma growth factor midkine as a prognostic growth factor. Tumors of the central nervous system (2012)
  • Author(s): Kishida S, Ikematsu S, Takei Y, Kadomatsu K
  • Publisher: Springer社(未定)
• [Patent(Industrial Property Rights)] 脂肪組織由来間葉系幹細胞を含有する、前立腺癌治療用細胞製剤 (2010)
  • Inventor(s): 山本徳則、小出直史、後藤百万、武井佳史
  • Industrial Property Rights Holder: 国立大学法人名古屋大学
  • Filing Date: 2010-12-03
  • Overseas
• [Patent(Industrial Property Rights)] 脂肪組織由来間葉系幹細胞を含有する、勃起不全又は尿意障害用の細胞製剤 (2010)
  • Inventor(s): 山本徳則、小出直史、武井佳史、松川宣久、舟橋康人、後藤百万
  • Industrial Property Rights Holder: 国立大学法人名古屋大学
  • Acquisition Date: 2010-09-07
  • Overseas
• [Patent(Industrial Property Rights)] 脂肪組織由来間葉系幹細胞を含有する前立腺癌治療用細胞製剤 (2009)
  • Inventor(s): 山本徳則、小出直史、後藤百万、武井佳史
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Number: 2009-277437
  • Filing Date: 2009-12-07