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gene therapy using siena technology

Research Project

Project/Area Number 23792014
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionNippon Medical School

Principal Investigator

IGARASHI Tsutomu  日本医科大学, 医学部, 講師 (10421190)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords網膜 / 遺伝子治療 / AAVベクター / siRNA / VEGF / 脈絡膜新生血管 / 血管新生 / 眼科 / 新生血管 / 抑制 / 遺伝子 / ウィルスベクター
Research Abstract

To assess the feasibility of a gene therapeutic approach to treating choroidal neovascularization (CNV), we generated an adeno-associated virus type 8 vector (AAV8) encoding a small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF), and determined its ability to inhibit angiogenesis. We made AAV8/SmVEGF-2. We injected AAV8/SmVEGF-2 or control vector (AAV8/GFP) into the subretinal space in C57BL/6 mice. The eyes were removed for flat mount analysis of CNV surface area. Subretinal delivery of AAV8/SmVEGF-2 significantly diminished CNV at the laser lesions, as compared to AAV8/GFP Using ELISA, we found that VEGF levels were reduced by approximately half in AAV8/SmVEGF-2 treated eyes. These results suggest that siRNA-VEGF can be expressed across the retina and that long-term suppression of CNV is possible through the use of stable AAV-mediated siRNA-VEGF expression.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (45 results)

All 2014 2013 2012 2011

All Journal Article (28 results) (of which Peer Reviewed: 14 results) Presentation (17 results)

  • [Journal Article] AAV2/8-mediated expression of siRNA targeting VEGF efficiently inhibits neovascularization in a murine choroidal neovascularization model2014

    • Author(s)
      Igarashi T, Miyake N, Fujimoto C, Yaguchi C, Iijima O, Shimada T, Takahashi H, Miyake K
    • Journal Title

      Molecular Vision

      Volume: 20 Pages: 488-496

    • Related Report
      2013 Final Research Report
  • [Journal Article] Temperature in the anterior chamber during phacoemulsification2014

    • Author(s)
      Suzuki H, Oki K, Igarashi T, Shiwa T, Takahashi H
    • Journal Title

      J Cataract Refract Surg

    • Related Report
      2013 Final Research Report
  • [Journal Article] 自発的開瞼維持による涙液浸透圧の変化2014

    • Author(s)
      一戸唱、五十嵐勉、藤本千明、飯島修、小野眞史、高橋浩
    • Journal Title

      あたらしい眼科2014

      Volume: 31(2) Pages: 257-259

    • NAID

      40019989502

    • Related Report
      2013 Final Research Report
  • [Journal Article] Temperature in the anterior chamber during phacoemulsification.2014

    • Author(s)
      Suzuki H, Oki K, Igarashi T, Shiwa T, Takahashi H.
    • Journal Title

      J Cataract Refract Surg

      Volume: 27

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AAV2/8-mediated expression of siRNA targeting VEGF efficiently inhibits neovascularization in a murine choroidal neovascularization model.2014

    • Author(s)
      Igarashi T, Miyake N, Fujimoto C, Yaguchi C, Iijima O, Shimada T, Takahashi H, Miyake K.
    • Journal Title

      Molecular Vision

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct comparison of the administration routes for AAV8-mediated ocular gene therapy2013

    • Author(s)
      Igarashi T, Miyake K, Asakawa N, Miyake N, Shimada T, Takahashi H
    • Journal Title

      Current eye research

      Volume: 38(5) Pages: 569-577

    • Related Report
      2013 Final Research Report
  • [Journal Article] Simultaneous treatment of pterygium and temporal conjunctivochalasis2013

    • Author(s)
      Suzuki H, Shiwa T, Oharazawa H, Igarashi T, Takahashi H
    • Journal Title

      Journal of Nippon Medical School

      Volume: 80(1) Pages: 74-77

    • NAID

      130004147209

    • Related Report
      2013 Final Research Report
  • [Journal Article] Intravenous cyclophosphamide pulse therapy in Japanese children with systemic lupus erythematosus2013

    • Author(s)
      Igarashi T, Igarashi T, Shimizu A, Itoh Y
    • Journal Title

      Journal of Nippon Medical School

      Volume: 80(5) Pages: 396-400

    • NAID

      130004147255

    • Related Report
      2013 Final Research Report
  • [Journal Article] Seroconversion of hepatitis B envelope antigen by entecavir in a child with hepatitis B virus–related membranous nephropathy2013

    • Author(s)
      Igarashi T, Shimizu A, Igarashi T, Hanaoka K, Yoshizaki K, Shigemori T, Shimizu S, Komeichi H, Itoh Y
    • Journal Title

      Journal of Nippon Medical School

      Volume: 80(5) Pages: 387-395

    • NAID

      130004147254

    • Related Report
      2013 Final Research Report
  • [Journal Article] A definitive diagnosis of mucosa-associated lymphoid tissue lymphoma made at a second biopsy examination2013

    • Author(s)
      Igarashi T, Shimizu A, Yamaguchi H, Fukushima Y, Igarashi T, Takahashi H
    • Journal Title

      Journal of Nippon Medical School

      Volume: 80 (6) Pages: 475-480

    • Related Report
      2013 Final Research Report
  • [Journal Article] Direct comparison of the administration routes for AAV8-mediated ocular gene therapy.2013

    • Author(s)
      Igarashi T, Miyake K, Asakawa N, Miyake N, Shimada T, Takahashi H.
    • Journal Title

      Current eye research

      Volume: 38 Pages: 569-77

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous treatment of pterygium and temporal conjunctivochalasis.2013

    • Author(s)
      Suzuki H, Shiwa T, Oharazawa H, Igarashi T, Takahashi H.
    • Journal Title

      Journal of Nippon Medical School.

      Volume: 80 Pages: 74-77

    • NAID

      130004147209

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intravenous cyclophosphamide pulse therapy in Japanese children with systemic lupus erythematosus.2013

    • Author(s)
      Igarashi T, Igarashi T, Shimizu A, Itoh Y.
    • Journal Title

      Journal of Nippon Medical School

      Volume: 80 Pages: 396-400

    • NAID

      130004147255

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Seroconversion of hepatitis B envelope antigen by entecavir in a child with hepatitis B virus–related membranous nephropathy.2013

    • Author(s)
      Igarashi T, Shimizu A, Igarashi T, Hanaoka K, Yoshizaki K, Shigemori T, Shimizu S, Komeichi H, Itoh Y.
    • Journal Title

      Journal of Nippon Medical School

      Volume: 80 Pages: 387-395

    • NAID

      130004147254

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A definitive diagnosis of mucosa-associated lymphoid tissue lymphoma made at a second biopsy examination.2013

    • Author(s)
      Igarashi T, Shimizu A, Yamaguchi H, Fukushima Y, Igarashi T, Takahashi H.
    • Journal Title

      Journal of Nippon Medical School

      Volume: 80 Pages: 475-480

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct comparison of the administration routes for AAV8-mediated ocular gene therapy.2013

    • Author(s)
      Igarashi T, Miyake K, Asakawa N, Miyake N, Shimada T, Takahashi T.
    • Journal Title

      Current eye research

      Volume: in press Pages: 0-0

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid and Transient Upregulation of CCL11 (Eotaxin-1) in Mouse Ovary During Terminal Stages of Follicular Development2012

    • Author(s)
      Kuwabara Y, Katayama A, Igarashi T, Tomiyama R, Piao H, Kaneko R, Abe T, Mine K, Akira S, Orimo H, Takeshita T
    • Journal Title

      Am J Reprod Immunol

      Volume: 67(5) Pages: 358-368

    • Related Report
      2013 Final Research Report
  • [Journal Article] A case of juvenile Sjögren's syndrome with interstitial nephritis2012

    • Author(s)
      Igarashi T, Itoh Y, Shimizu A, Igarashi T, Yoshizaki K, Fukunaga Y
    • Journal Title

      Journal of Nippon Medical School

      Volume: 79(4) Pages: 286-290

    • NAID

      130004147180

    • Related Report
      2013 Final Research Report
  • [Journal Article] Mometasone Furoate Nasal Spray Relieves the Ocular Symptoms of Seasonal Allergic Rhinoconjunctivitis2012

    • Author(s)
      Igarashi T, Nakazato Y, Kunishige T, Fujita M, Yamada Y, Fujimoto C, Okubo K, Takahashi H
    • Journal Title

      Journal of Nippon Medical School

      Volume: 79 (3) Pages: 182-189

    • NAID

      130004147162

    • Related Report
      2013 Final Research Report
  • [Journal Article] A new mutation in RP1L1 gene in occult macular dystrophy patient associated with a depolarizing-pattern of focal macular ERG2012

    • Author(s)
      Kabuto T, Takahashi H, Goto-Fukuura Y, Igarashi T, Akahori M, Kameya S, Iwata T, Mizota A, Yamaki K, Miyake Y, Takahashi H
    • Journal Title

      Molecular Vision

      Volume: 18 Pages: 1031-1039

    • Related Report
      2013 Final Research Report
  • [Journal Article] Mean hemoglobin levels in venous blood samples and prevalence of anemia in Japanese elementary and junior high school students2012

    • Author(s)
      Igarashi T, Itoh Y, Maeda M, Igarashi T, Fukunaga Y
    • Journal Title

      Journal of Nippon Medical School

      Volume: 79 (3) Pages: 232-235

    • NAID

      130004147171

    • Related Report
      2013 Final Research Report
  • [Journal Article] 強皮症に随伴した両眼性汎ぶどう膜炎の1例2012

    • Author(s)
      佐藤景子、堀純子、五十嵐勉、今高之
    • Journal Title

      臨床眼科

      Volume: 66(2) Pages: 179-183

    • Related Report
      2013 Final Research Report
  • [Journal Article] Rapid and Transient Upregulation of CCL11 (Eotaxin-1) in Mouse Ovary During Terminal Stages of Follicular Development.2012

    • Author(s)
      Kuwabara Y, Katayama A, Igarashi T, Tomiyama R, Piao H, Kaneko R, Abe T, Mine K, Akira S, Orimo H, Takeshita T.
    • Journal Title

      Am J Reprod Immunol.

      Volume: 67 Pages: 358-68

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of juvenile Sjögren’s syndrome with interstitial nephritis.2012

    • Author(s)
      Igarashi T, Itoh Y, Shimizu A, Igarashi T, Yoshizaki K, Fukunaga Y.
    • Journal Title

      Journal of Nippon Medical School.

      Volume: 79 Pages: 286-90

    • NAID

      130004147180

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mometasone Furoate Nasal Spray Relieves the Ocular Symptoms of Seasonal Allergic Rhinoconjunctivitis.2012

    • Author(s)
      Igarashi T, Nakazato Y, Kunishige T, Fujita M, Yamada Y, Fujimoto C, Okubo K, Takahashi H.
    • Journal Title

      Journal of Nippon Medical School.

      Volume: 79 Pages: 182-189

    • NAID

      130004147162

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A new mutation in RP1L1 gene in occult macular dystrophy patient associated with a depolarizing-pattern of focal macular ERG.2012

    • Author(s)
      Kabuto T, Takahashi H, Goto-Fukuura Y, Igarashi T, Akahori M, Kameya S, Iwata T, Mizota A, Yamaki K, Miyake Y, Takahashi H.
    • Journal Title

      Molecular Vision.

      Volume: 18 Pages: 1031-9

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mean hemoglobin levels in venous blood samples and prevalence of anemia in Japanese elementary and junior high school students.2012

    • Author(s)
      Igarashi T, Itoh Y, Maeda M, Igarashi T, Fukunaga Y.
    • Journal Title

      Journal of Nippon Medical School

      Volume: 79 Pages: 232-235

    • NAID

      130004147171

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mometasone Furoate Nasal Spray Relieves the Ocular Symptoms of Seasonal Allergic Rhinoconjunctivitis2011

    • Author(s)
      Igarashi T
    • Journal Title

      Journal of Nippon Medical School

      Volume: in press

    • NAID

      130004147162

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 短時間の超高浸透圧暴露で角膜上皮細胞からのIL-6産生は上昇する2014

    • Author(s)
      小林舞香、五十嵐勉、藤本千明、高橋浩
    • Organizer
      日本角膜学会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Final Research Report
  • [Presentation] レバミピド点眼によるドライアイの自覚症状・他覚所見の改善2014

    • Author(s)
      仲野裕一郎、五十嵐勉、藤田美穂、山田佑美、藤本千明、國重智之、高橋永幸、高橋浩
    • Organizer
      日本角膜学会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Final Research Report
  • [Presentation] 白内障手術前後における涙液浸透圧の変化2014

    • Author(s)
      有馬武志、五十嵐勉、藤田美穂、山田佑美、藤本千明、高橋永幸、國重智之、高橋浩
    • Organizer
      日本角膜学会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Final Research Report
  • [Presentation] 血漿浸透圧と涙液浸透圧の相関因子について2014

    • Author(s)
      久保田大紀、五十嵐勉、藤田美穂、山田佑美、藤本千明、国重智之、高橋永幸、高橋浩
    • Organizer
      日本角膜学会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Final Research Report
  • [Presentation] Adeno-associated vector (type 8)-mediated expression of siRNA targeting vascular endothelial growth factor efficiently inhibits neovascularization in a murine choroidal neovascularization model2014

    • Author(s)
      Igarashi T, Miyake K, Miyake N, Iijima O, Yaguchi C, Yaguchi C, Shimada T, Takahashi H
    • Organizer
      World ophthalmology congress
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Final Research Report
  • [Presentation] A definitive diagnosis of mucosa-associated lymphoid tissue lymphoma made at a second biopsy examination2014

    • Author(s)
      Takahashi K, Igarashi T, Shimizu A, Yamaguchi A, Fukushima Y, Igarashi T, Akeo K, Takahashi H
    • Organizer
      World ophthalmology congress
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Final Research Report
  • [Presentation] Alteration of tear osmolality by sustained eye opening2014

    • Author(s)
      Ichinohe S, Igarashi T, Fujimoto C, Ono M, Takahashi H
    • Organizer
      World ophthalmology congress
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Final Research Report
  • [Presentation] Adeno-associated vector (type 8)-mediated expression of siRNA targeting vascular endothelial growth factor efficiently inhibits neovascularization in a murine choroidal neovascularization model2013

    • Author(s)
      Igarashi T, Miyake K, Miyake N, Iijima O, Yaguchi C, Shimada T, Takahashi H
    • Organizer
      American society of gene therapy
    • Place of Presentation
      Solt lake city
    • Related Report
      2013 Final Research Report
  • [Presentation] siRNA targeting vascular endothelial growth factor by adeno-associated vector (type 8) efficiently inhibits neovascularization in a murine choroidal neovascularization model2013

    • Author(s)
      Igarashi T, Miyake N, Iijima O, Yaguchi C, Shimada T, Takahashi H, Miyake K
    • Organizer
      Japan society of gene therapy (18th)
    • Place of Presentation
      Okayama
    • Related Report
      2013 Final Research Report
  • [Presentation] siRNA targeting vascular endothelial growth factor by adeno-associated vector (type 8) efficiently inhibits neovascularization in a murine choroidal neovascularization model2013

    • Author(s)
      Igarashi T, Miyake N, Iijima O, Yaguchi C, Shimada T, Takahashi H、Miyake K
    • Organizer
      日本網膜硝子体学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Bone Marrow Cell Based Enzyme Replacement Prolongs Survival and Improves Disease Phenotypes In a Mouse Model Of Lethal Hypophosphatasia2013

    • Author(s)
      Iijima O, Miyake K, Nakamura A, Igarashi T, Kanokoda C, Watanabe A, Shimada T
    • Organizer
      American society of hematology
    • Place of Presentation
      New Orieans
    • Related Report
      2013 Final Research Report
  • [Presentation] 自発的開瞼維持による涙液浸透圧の変化2013

    • Author(s)
      一戸唱、五十嵐勉、飯島修、小野眞史、高橋浩
    • Organizer
      日本角膜学会
    • Place of Presentation
      和歌山
    • Related Report
      2013 Final Research Report
  • [Presentation] 低フォスファターゼ症マウスに対するex vivo遺伝子治療法の検討2013

    • Author(s)
      飯島修、三宅弘一、中村有希、鹿子田千津、五十嵐勉、渡邉淳、島田隆
    • Organizer
      第58回日本人類遺伝学会学術集会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] Rescue of Lethal Hypophosphatasia Mice by Neonatal Ex Vivo Gene Therapy Using Lentivirally Transduced Bone Marrow Cells2012

    • Author(s)
      Iijima O, Miyake K, Sugano-Tajima H, Igarashi T, Kanokoda C, Watanabe A, Shimada T
    • Organizer
      American society of hematology
    • Place of Presentation
      Atlanta
    • Related Report
      2013 Final Research Report
  • [Presentation] 異なる投与法によるAAVtype8ベクターの遺伝子導入効率と安全性の比較検討2012

    • Author(s)
      五十嵐勉、三宅弘一、浅川なぎさ、三宅紀子、島田隆、高橋浩
    • Organizer
      日本網膜硝子体学会
    • Related Report
      2013 Final Research Report
  • [Presentation] Rescue of Lethal Hypophosphatasia Mice by Neonatal Ex Vivo Gene Therapy Using Lentivirally Transduced Bone Marrow Cells.2012

    • Author(s)
      Osamu Iijima, Koichi Miyake, Hanako Sugano-Tajima, Tsutomu Igarashi, Chizu Kanokoda, Atsushi Watanabe and Takashi Shimada.
    • Organizer
      American society of hematology
    • Place of Presentation
      アトランタ
    • Related Report
      2012 Research-status Report
  • [Presentation] Direct Comparison of Administration Routes for AAV 8 Mediated Ocular Gene Therapy.2011

    • Author(s)
      Igarashi T
    • Organizer
      American society of gene therapy.
    • Place of Presentation
      Washington State Convention & Trade Center, Seattle, WA, USA
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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