Perinatal gene therapy for severe genetic diseases

• Project/Area Number: 22390212
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nippon Medical School
• Principal Investigator: SHIMADA Takashi 日本医科大学, 大学院・医学研究科, 教授 (20125074)
• Co-Investigator(Renkei-kenkyūsha): MIYAKE Koichi 日本医科大学, 医学部, 准教授 (90267211) ; MIGITA Makoto 日本医科大学, 医学部, 准教授 (50256963) ; WATANABE Atsushi 日本医科大学, 医学部, 准教授 (10307952)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 遺伝子 / 遺伝子治療 / 遺伝病

Research Abstract

We investigated the feasibility of prenatal/neonatal gene therapy of both metachromatic leukodystrophy (MLD) and hypophosphatasia (HPP) model mice using adeno-associated viral (AAV) vectors. After intravenous injection of AAV vector into neonatal MLD mice, global gene transfer into the brain across the BBB and long term gene expression without immune reaction were detected. Significant improvement of neurological symptoms was observed after treatment. The fetuses of HPP mice underwent transuterine intraperitoneal injection of AAV vector. Live-born mice showed improved mineralization, phenotypic correction and prolonged survival. These data demonstrated that systemic injection of AAV vector in the perinatal period is an effective strategy for the treatment of severe genetic diseases such as MLD and HPP.

Research Products

• [Journal Article] Direct Comparison of 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 Res. Volume: (in press)
• [Journal Article] 5'-HS4 core insulator blocks promoter interference in the lentivirus vector including the MSCV-U3 and EF1α double internal promoters. (2013)
  • Author(s): Uchida, N., Hanawa, H., Yamamoto, M., Shimada, T.
  • Journal Title: Hum. Gene Ther. Volume: (in press)
• [Journal Article] AAV-8 vector expressing IL-24 efficiently suppresses tumor growth mediated by specific mechanisms inMLL/AF4-positive ALL model mice. (2012)
  • Author(s): Tamai, H., Miyake, K., Yamaguchi, H., Takatori, M., Dan, K., Inokuchi, K., Shimada, T.
  • Journal Title: Blood Volume: 119 Pages: 64-71
• [Journal Article] Successful gene therapy in utero for lethal murine hypophosphatasia. (2012)
  • Author(s): Sugano, H., Matsumoto, T., Miyake, K., Watanabe, A., Iijima, O., Migita, M., Narisawa, S., Millan, J.L., Fukunaga, Y., Shimada, T.
  • Journal Title: Hum. Gene Ther. Volume: 23 Pages: 399-406
• [Journal Article] Serotype-independent method of recombinant adeno-associated virus (AAV) vector production and purification. (2012)
  • Author(s): Miyake, K., Miyake, N., Yamazaki, Y., Shimada, T., Hirai, Y.
  • Journal Title: J Nippon Med Sch. Volume: 79 Pages: 394-402
  • NAID: 130004057397
• [Journal Article] AAV-8 vector expressing IL-24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice. (2012)
  • Author(s): Tamai, H.
  • Journal Title: Blood Volume: 119 Issue: 1 Pages: 64-71
  • DOI: 10.1182/blood-2011-05-354050
  • Peer Reviewed
• [Journal Article] Successful gene therapy in utero for lethal murine hypophosphatasia. (2012)
  • Author(s): Sugano, H.
  • Journal Title: Hum. Gene Ther. Volume: 23 Issue: 4 Pages: 399-406
  • DOI: 10.1089/hum.2011.148
  • Peer Reviewed
• [Journal Article] Identical germline mutations in the TMEM127 gene in 2 unrelated Japanese patients with bilateral pheochromocytoma. (2012)
  • Author(s): Takeichi, N.
  • Journal Title: Clini Endocrinol. Volume: 77 Issue: 5 Pages: 707-714
  • DOI: 10.1111/j.1365-2265.2012.04421.x
  • Peer Reviewed
• [Journal Article] Ehlers-Danlos Syndrome, Vascular Type: A Novel Missense Mutation in COL3A1 Gene. (2012)
  • Author(s): Masuno, M.
  • Journal Title: Congenit Anom. Volume: 52 Issue: 4 Pages: 207-210
  • DOI: 10.1111/j.1741-4520.2011.00353.x
  • Peer Reviewed
• [Journal Article] Prolonged survival and phenotypic correction of Akp2-/- hypophosphatasia mice by lentiviral gene therapy. (2011)
  • Author(s): Yamamoto, S., Orimo, H., Matsumoto, T., Iijima, O., Narisawa, S., Maeda, T., Millan, J., Shimada, T.
  • Journal Title: J. Bone Miner. Res. Volume: 26 Pages: 135-142
• [Journal Article] A lentiviral strategy for highly efficient retrograde gene transfer by pseudotyping with fusion envelope glycoprotein. (2011)
  • Author(s): Kato, S., Kobayashi, K., Inoue, K., Kuramochi, M., Okada, T., Yaginuma, H., Morimoto, K., Shimada, T., Takada, M., Kobayashi, K.
  • Journal Title: Hum. Gene Ther. Volume: 22 Pages: 197-206
• [Journal Article] In Vivo Application of an RNAi Strategy for the Selective Suppression of aMutant Allele. (2011)
  • Author(s): Kubodera, T., Yamada, H., Anzai, M., Ohira, S., Yokota, S., Hirai, Y., Mochizuki, H., Shimada, T., Mitani, T., Mizusawa, H., Yokota, T.
  • Journal Title: Hum. Gene Ther. Volume: 22 Pages: 27-34
• [Journal Article] Prevalence of c.1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasia in Japanese and effects of the mutation on heterozygous carriers. (2011)
  • Author(s): Watanabe A, Karasugi T, Sawai H, Banyar Tang Naing, Ikegawa S, Orimo H, Shimada S.
  • Journal Title: J Hum Genet Volume: 56 Pages: 166-168
  • NAID: 10030658012
• [Journal Article] Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles. (2011)
  • Author(s): Mayra, A., Tomimitsu, H., Kubodera, T., Kobayashi, M., Piao, W., Sunaga, F., Hirai, Y., Shimada, T., Mizusawa, H., Yokota, T.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 405 Pages: 204-209
• [Journal Article] Global gene transfer into the CNS across the BBB after neonatal systemic delivery of single-stranded AAV vectors. (2011)
  • Author(s): Miyake, N., Miyake, K., Yamamoto, M., Hirai, Y., Shimada, T.
  • Journal Title: Brain Res. Volume: 1389 Pages: 19-26
• [Journal Article] Rescue of Severe Infantile Hypophosphatasia Mice by AAV Mediated Sustained Expression of Soluble Alkaline Phosphatase. (2011)
  • Author(s): Matsumoto, T., Miyake, K., Yamamoto, S., Orimo, H., Miyake, N., Odagaki, Y.,Adachi, K., Iijima, O., Narisawa, S., Millan, J.L., Fukunaga, Y., Shimada, T.
  • Journal Title: Hum. Gene Ther. Volume: 22 Pages: 1355-1364
• [Journal Article] Direct comparison of four adeno-associated virus serotypes in mediating the production of anti-angiogenic proteins in mouse muscle. (2011)
  • Author(s): Isotani, M., Miyake, K., Miyake, N., Hirai, Y., Shimada, T.
  • Journal Title: Cancer Invest. Volume: 29 Pages: 353-359
• [Journal Article] Neuron-Specific Gene Transfer through Retrograde Transport of Lentiviral Vector Pseudotyped with a Novel Type of Fusion Envelope Glycoprotein. (2011)
  • Author(s): Kato, S., Kuramochi, M., Takasumi, K., Kobayashi, K., Inoue, K., Takahara, D., Hitoshi, S., Takenaka, K., Shimada, T., Takada, M., Kobayashi, K.
  • Journal Title: Hum. Gene Ther. Volume: 22 Pages: 1511-1523
• [Journal Article] Adeno-associated viral vector-mediated gene transduction in mesencephalic slice culture. (2011)
  • Author(s): Nihira, T., Yasuda, T., Hirai, Y., Shimada, T., Mizuno, Y., Mochizuki, H.
  • Journal Title: J Neurosci Methods. Volume: 201 Pages: 55-60
• [Journal Article] Overexpression of GDNF in the Uninjured DRG Exerts Analgesic Effects on Neuropathic Pain Following Segmental Spinal Nerve Ligation in Mice. (2011)
  • Author(s): Takasu, K., Sakai, A., Hanawa, H., Shimada, T., Suzuki, H.
  • Journal Title: J. Pain Volume: 12 Pages: 1130-1139
• [Journal Article] Prolonged survival and phenotypic correction of Akp2^<-/->hypophosphatasia mice by lentiviral gene therapy (2011)
  • Author(s): Yamamoto, S.
  • Journal Title: J.Bone Miner.Res. Volume: 26 Pages: 135-142
  • Peer Reviewed
• [Journal Article] A lentiviral strategy for highly efficient retrograde gene transfer by pseudotyping with fusion envelope glycoprotein (2011)
  • Author(s): Kato, S.
  • Journal Title: Hum.Gene Ther. Volume: 22 Pages: 197-206
  • Peer Reviewed
• [Journal Article] In Vivo Application of an RNAi Strategy for the Selective Suppression of a Mutant Allele (2011)
  • Author(s): Kubodera, T.
  • Journal Title: Hum.Gene Ther. Volume: 22 Pages: 27-34
  • Peer Reviewed
• [Journal Article] Prevalence of c.1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasia in Japanese and effects of the mutation on heterozygous carriers (2011)
  • Author(s): Watanabe A.
  • Journal Title: J Hum Genet Volume: 56 Pages: 166-168
  • NAID: 10030658012
  • Peer Reviewed
• [Journal Article] Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles (2011)
  • Author(s): Mayra, A.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 405 Pages: 204-209
  • Peer Reviewed
• [Journal Article] A novel mutation screening system for Ehlers-Danlos Syndrome, vascular type by high-resolution melting curve analysis in combination with small amplicon genotyping using genomic DNA (2011)
  • Author(s): Naing, BT.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 405 Pages: 368-372
  • Peer Reviewed
• [Journal Article] Parkin-Mediated Protection of Dopaminergic Neurons in a Chronic MPTP-Minipump Mouse Model of Parkinson Disease (2011)
  • Author(s): Yasuda, T.
  • Journal Title: J Neuropathol Exp Neurol. Volume: 70 Pages: 686-697
  • Peer Reviewed
• [Journal Article] Global gene transfer into the CNS across the BBB after neonatal systemic delivery of single-stranded AAV vectors (2011)
  • Author(s): Miyake, N.
  • Journal Title: Brain Res. Volume: 1389 Pages: 19-26
  • Peer Reviewed
• [Journal Article] Rescue of Severe Infantile Hypophosphatasia Mice by AAV Mediated Sustained Expression of Soluble Alkaline Phosphatase (2011)
  • Author(s): Matsumoto, T.
  • Journal Title: Hum.Gene Ther. Volume: 22 Pages: 1355-1364
  • Peer Reviewed
• [Journal Article] Direct comparison of four adeno-associated virus serotypes in mediating the production of anti-angiogenic proteins in mouse muscle (2011)
  • Author(s): Isotani, M.
  • Journal Title: Cancer Invest. Volume: 29 Pages: 353-359
  • Peer Reviewed
• [Journal Article] Neuron-Specific Gene Transfer through Retrograde Transport of Lentiviral Vector Pseudotyped with a Novel Type of Fusion Envelope Glycoprotein (2011)
  • Author(s): Kato, S.
  • Journal Title: Hum.Gene Ther. Volume: 22 Pages: 1511-1523
  • Peer Reviewed
• [Journal Article] Adeno-associated viral vector-mediated gene transduction in mesencephalic slice culture (2011)
  • Author(s): Nihira, T.
  • Journal Title: J Neurosci Methods. Volume: 201 Pages: 55-60
  • Peer Reviewed
• [Journal Article] Activated K-Ras protein accelerates human MLL/AF4-induced leukemo-lymphomogenicity in a transgenic mouse model (2011)
  • Author(s): Tamai, H.
  • Journal Title: Leukemia Volume: 25 Pages: 888-891
  • Peer Reviewed
• [Journal Article] Resistance of MLL/AF4-positive acute lymphoblastic leukemia to tumornecrosis factor-alpha is mediated by S100A6 up-regulation (2011)
  • Author(s): Tamai, H.
  • Journal Title: Blood Cancer J. Volume: 1
  • Peer Reviewed
• [Journal Article] Overexpression of GDNF in the Uninjured DRG Exerts Analgesic Effects on Neuropathic Pain Following Segmental Spinal Nerve Ligation in Mice (2011)
  • Author(s): Takasu, K.
  • Journal Title: J.Pain Volume: 12 Pages: 1130-1139
  • Peer Reviewed
• [Journal Article] Prolonged survival and phenotypic correction of Akp2^<-/-> hypophosphatasia mice by lentiviral gene therapy. (2011)
  • Author(s): Yamamoto, S.
  • Journal Title: J.Bone Miner.Res. Volume: 26 Pages: 135-142
  • Peer Reviewed
• [Journal Article] A lentiviral strategy for highly efficient retrograde gene transfer by pseudotyping with fusion envelope glycoprotein. (2011)
  • Author(s): Kato, S.
  • Journal Title: Hum.Gene Ther. Volume: 22 Pages: 197-206
  • Peer Reviewed
• [Journal Article] In Vivo Application of an RNAi Strategy for the Selective Suppression of a Mutant Allele. (2011)
  • Author(s): Kubodera, T.
  • Journal Title: Hum.Gene Ther. Volume: 22 Pages: 27-34
  • Peer Reviewed
• [Journal Article] Prevalence of c.1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypopho sphatasia in Japanese and effects of the mutation on heterozygous carriers. (2011)
  • Author(s): Watanabe, A.
  • Journal Title: J Hum Genet. Volume: 56 Pages: 166-168
  • NAID: 10030658012
  • Peer Reviewed
• [Journal Article] Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles. (2011)
  • Author(s): Mayra, A.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 405 Pages: 204-209
  • Peer Reviewed
• [Journal Article] A novel mutation screening system for Ehlers-Danlos Syndrome vascular type by high-resolution melting curve analysis in combination with small amplicon genotyping using genomic DNA. (2011)
  • Author(s): Naing, BT.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 405 Pages: 368-372
  • Peer Reviewed
• [Journal Article] Global gene transfer into the CNS across the BBB after neonatal systemic delivery of single-stranded AAV vectors. (2011)
  • Author(s): Miyake, N.
  • Journal Title: Brain Res. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Rescue of Severe Infantile Hypophosphatasia Mice by AAV Mediated Sustained Expression of Soluble Alkaline Phosphatase. (2011)
  • Author(s): Matsumoto, T.
  • Journal Title: Hum.Gene Ther. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Direct comparison of four adeno-associated virus serotypes in mediating the production of anti-angiogenic proteins in mouse muscle. (2011)
  • Author(s): Isotani, M.
  • Journal Title: Cancer Invest. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Hematopoiesis in regenerated bone marrow within hydroxyapatite scaffold. (2010)
  • Author(s): Fujita, A., Migita, M., Ueda, T., Ogawa, R., Fukunaga, Y., Shimada, T.
  • Journal Title: Pediatr. Res. Volume: 68 Pages: 35-40
• [Journal Article] Adeno-associated vector (type8)-mediated expression of soluble Flt-1 efficiently inhibits neovascularization in a murine choroidalneovascularization model. (2010)
  • Author(s): Igarashi, T., Miyake, K., Masuda, I., Takahashi, H., Shimada, T.
  • Journal Title: Hum. Gene Ther. Volume: 21 Pages: 631-637
• [Journal Article] Successful treatment of metachromatic leukodystrophy using bone marrow transplantation of HoxB4 overexpressing cells. (2010)
  • Author(s): Miyake, N., Miyake, K., Karlsson, S., Shimada, T.
  • Journal Title: Mol. Ther. Volume: 18 Pages: 1373-1378
• [Journal Article] Circadian disruption accelerates tumor growth and angio/stromagenesis through a Wnt signaling pathway. (2010)
  • Author(s): Yasuniwa, Y., Izumi, H., Wang, K-Y., Shimajiri, S., Sasaguri, Y., Kawai, K., Kasai, H., Shimada, T., Miyake,. K., Kashiwagi, E., Hirano, G., Kidani, A.,Akiyama, M., Han, B., Wu, Y., Ieiri, I., Higuchi, S., Kohno, K.
  • Journal Title: PloS ONE Volume: 5
• [Journal Article] Hematopoiesis in regenerated bone marrow within hydroxyapatite scaffold. (2010)
  • Author(s): Fujita, A.
  • Journal Title: Pediatr.Res. Volume: 68 Pages: 35-40
  • Peer Reviewed
• [Journal Article] Adeno-associated vector (type 8)-mediated expression of soluble Flt-1 efficiently inhibits neovascularization in a murine choroidal neovascularization model. (2010)
  • Author(s): Igarashi, T.
  • Journal Title: Hum.Gene Ther. Volume: 21 Pages: 631-637
  • Peer Reviewed
• [Journal Article] Successful treatment of metachromatic leukodystrophy using bone marrow transplantation of HoxB4 overexpressing cells. (2010)
  • Author(s): Miyake, N.
  • Journal Title: Mol.Ther. Volume: 18 Pages: 1373-1378
  • Peer Reviewed
• [Journal Article] Circadian disruption accelerates tumor growth and angio/stromagenesis through a Wnt signaling pathway. (2010)
  • Author(s): Yasuniwa, Y.
  • Journal Title: PloS ONE. Volume: 5 Pages: 15330-15330
  • Peer Reviewed
• [Journal Article] Cyclical mechanical stretch enhances degranulation and IL-4 secretion in RBL-2H3 mast cells.
  • Author(s): Komiyama, H., Miyake, K., Asai, K., Mizuno, K., Shimada, T.
  • Journal Title: Cell Biochem. Function Volume: (in press)
• [Presentation] Gene therapy of adult MLD model mice by intrathecal administration of type 9 AAV vector. (2012)
  • Author(s): Miyake, N., Miyake, K., Sakai, A., Yamamoto, M., Endo, A., Suzuki, H., Shimada, T.
  • Organizer: 15th Annual Meeting of the American Society of Gene & Cell Therapy.
  • Place of Presentation: Philadelphia, Pennsylvania
• [Presentation] Gene therapy for lethalmurine hyopophosphatasia. (2012)
  • Author(s): Shimada T
  • Organizer: 6th International Alkaline Phosphatase And Hypophosphatasia Symposium.
  • Place of Presentation: Huningue, Alsace, France
• [Presentation] AAV9 mediated gene therapy of MLD model mice. (2012)
  • Author(s): Miyake, N., Miyake, K., Sakai, A., Yamamoto, M., Endo, A., Suzuki, H., Shimada, T.
  • Organizer: 20th Annual Meeting of the European Society of Gene & Cell Therapy.
  • Place of Presentation: Versailles, France
• [Presentation] DRG神経におけるmiR-7a過剰発現は神経障害性疼痛を特異的に抑制する. (2012)
  • Author(s): 坂井 敦
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] 低フォスファターゼ症モデルマウスの胎児期遺伝子治療 (2011)
  • Author(s): 菅野華子
  • Organizer: 第53回日本先天代謝異常学会総会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-24
• [Presentation] The effect and specific mechanisms of systemic gene therapy using AAV8-IL24 in MLL/AF4 Tg mice (2011)
  • Author(s): Tamai, H.
  • Organizer: 日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] 低フォスファターゼ症モデルマウスの胎児期遺伝子治療 (2011)
  • Author(s): 菅野華子
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-07-28
• [Presentation] 骨髄細胞移植による低フォスファターゼ症の遺伝子治療 (2011)
  • Author(s): 飯島修
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-07-28
• [Presentation] Gene Therapy for MLD by Intrathecal Administration of Type 9 AAV Vector Expressing ASA (2011)
  • Author(s): Miyake, N.
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-17
• [Presentation] Direct comparison of administration routes for AAV8 mediated ocular gene therapy (2011)
  • Author(s): Asakawa, N.
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-17
• [Presentation] Successful treatment of severe infantile hypophosphatasia by ex vivo gene therapy using bone marrow cells expressing bone targeted TNALP (2011)
  • Author(s): Osamu, I.
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-16
• [Presentation] Development of cell targeting strategy using HIV vector pseudtyped with HIV envelope (2011)
  • Author(s): Miyake, K.
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-15
• [Presentation] A single injection of AAV-8 vector expressing IL-24 efficiently suppresses tumor growth mediated by multiple anti-tumor mechanisms in MLL/AF4 positive ALL model mice (2011)
  • Author(s): Tamai, H.
  • Organizer: 2011 European Hematology Association Congress
  • Place of Presentation: London
  • Year and Date: 2011-06-08
• [Presentation] Direct Comparison of Administration Routes for AAV 8 Mediated Ocular Gene Therapy (2011)
  • Author(s): IgarasM, T.
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Seattle
  • Year and Date: 2011-05-21
• [Presentation] Intrathecal Administration of Type 9 AAV Vector Expressing Arylsulfatase A Is Effective for Reduction of Sulfatide Storage but Not for Correction of Neurological Deficits in Adult Metachromatic Leukodystrophy Model Mice with Overt Neurological Symptoms (2011)
  • Author(s): Miyake, N.
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Seattle
  • Year and Date: 2011-05-21
• [Presentation] Successful Treatment of Hypophosphatasia Model Mice by a Single Intramuscular Injection of AAV Type 8 Vector Expressing Tissue-Nonspecific Alkaline Phosphatase (2011)
  • Author(s): Matsumoto, T.
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Seattle
  • Year and Date: 2011-05-20
• [Presentation] Fetal Gene Therapy for Lethal Murine Hypophosphatasia (2011)
  • Author(s): Sugano, H.
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Seattle
  • Year and Date: 2011-05-20
• [Presentation] AAVtype8ベクターの投与方法の違いによる遺伝子導入効率と発現期間の検討 (2011)
  • Author(s): 五十嵐勉
  • Organizer: 第115回日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-13
• [Presentation] Successful Treatment of Hypophosphatasia Model Mice by a Single Intramuscular Injection of AAV Type 8 Vector Expressing Tissue-Nonspecific Alkaline Phosphatase. (2011)
  • Author(s): Matsumoto, T., Miyake, K., Miyake, N., Orimo, H., Narisawa, S., Millan, J.L. Fukunaga, Y., Shimada. T.
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy.
  • Place of Presentation: Seattle, WA
• [Presentation] Fetal Gene Therapy for Lethal Murine Hypophosphatasia. (2011)
  • Author(s): Sugano, H., Matsumoto, T., Miyake, K., Watanabe, A., Narisawa, S.,Millan, J.L., Fukunaga, Y., Shimada, T.
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy.
  • Place of Presentation: Seattle, WA
• [Presentation] Direct Comparison of Administration Routes for AAV 8 Mediated Ocular Gene Therapy. (2011)
  • Author(s): Igarashi, T., Miyake, K., Asakawa, N., Shimada, T., Takahashi, H.
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy.
  • Place of Presentation: Seattle, WA
• [Presentation] IntrathecalAdministration of Type 9 AAV Vector Expressing Arylsulfatase A Is Effective for Reduction of Sulfatide Storage but Not for Correction of Neurological Deficits in Adult Metachromatic Leukodystrophy Model Mice with Overt Neurological Symptoms. (2011)
  • Author(s): Miyake, N., Miyake, K., Sakai, A., Yamamoto, M., Endo, A., Suzuki, H., Shimada, T.
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy.
  • Place of Presentation: Seattle, WA
• [Presentation] A single injection of AAV-8 vector expressing IL-24 efficiently suppressestumor growth mediated by multiple anti-tumor mechanisms in MLL/AF4 positive ALL model mice. (2011)
  • Author(s): Tamai, H., Miyake, K., Yamaguchi, H., Inokuchi, K., Shimada, T., Dan, K.
  • Organizer: 2011European Hematology AssociationCongress.
  • Place of Presentation: London
• [Presentation] AAV Type 8 Mediated Bone-Targeted and Muscle Directed Neonatal Gene Therapy for Hypophosphatasia (2011)
  • Author(s): Miyake, K.
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡(ポスター)
• [Presentation] 日本における周産期型低フォスファターゼ症高頻度変異部位1559delTと周産期時期からのfollow upの重要性 (2011)
  • Author(s): 渡邉淳
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪(ポスター)
• [Presentation] Type9アデノ随伴ウィルスベクター(AAV9)を用いたマウス胎児への遺伝子導入 (2010)
  • Author(s): 菅野華子
  • Organizer: ライソゾーム病研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-12-11
• [Presentation] A Single Intramuscular Injection of AAV-8 Vector Expressing MDA7/II-24 Efficiently Suppresses Tumor Growth Mediated by Multiple Anti-Cancer Mechanisms In Lymphoma Model Mice. (2010)
  • Author(s): Wang, N.
  • Organizer: 52nd American Society of Hematology Annual Meeting.
  • Place of Presentation: Orlando
  • Year and Date: 2010-12-05
• [Presentation] The Activated K-RAS Protein Accelerates Human Derived-MLL/AF4 Induced Leukemo-Lymphomogenicity In Transgenic Mice Model. (2010)
  • Author(s): Tamai H
  • Organizer: 52nd American Society of Hematology Annual Meeting.
  • Place of Presentation: Orlando
  • Year and Date: 2010-12-05
• [Presentation] MLL/AF4 Positive Acute Lymphoblastic Leukemia Has Resistance to Tumor Necrosis Factor-Alpha Caused by up-Regration of S100A6. (2010)
  • Author(s): Tamai H
  • Organizer: 52nd American Society of Hematology Annual Meeting.
  • Place of Presentation: Orlando
  • Year and Date: 2010-12-05
• [Presentation] ミトコンドリア呼吸鎖異常症の1例 (2010)
  • Author(s): 菅野華子
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-28
• [Presentation] Systemic injection of AAV type 9 in utero facilitates global gene expression in the CNS. (2010)
  • Author(s): Sugano, H.
  • Organizer: 18th European Society of Gene and Cell Therapy Annual Congress.
  • Place of Presentation: Milano, Italy
  • Year and Date: 2010-10-23
• [Presentation] Gene Therapy of Acute Lymphoblastic Leukemia with MLL/AF4 Using AAV8-IL24. (2010)
  • Author(s): Tamai, H.
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Establishment and Characterization of A New Lymphoid Malignancy Mouse Model Induced by the combination of MLL/AF4 and K-RAS. (2010)
  • Author(s): Tamai, H.
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Development of adeno-associated viral (AAV) vectormediated muscle directed systemic anti-angiogenic cancer gene therapy. (2010)
  • Author(s): Miyake K
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Widespread transduction in the cns and phenotypic correction of mld model mice by systemic neonatal injection of serotype 9 AAV vector. (2010)
  • Author(s): Miyake N
  • Organizer: The 16th Annual Meeting of Japan Society of Gene Therapy.
  • Place of Presentation: Tochigi
  • Year and Date: 2010-07-03
• [Presentation] Single injection of aav-8 vector expressing mda-7/i124 into muscle efficiently suppress tumor growth in lymphoma model mice. (2010)
  • Author(s): Wang N
  • Organizer: The 16th Annual Meeting of Japan Society of Gene Therapy.
  • Place of Presentation: Tochigi
  • Year and Date: 2010-07-02
• [Presentation] Establishment of aggressive m11/af4 induced lymphom a model mice through up-regulation of hoxa9 and s100 a6 expression. (2010)
  • Author(s): Tamai H
  • Organizer: The 16th Annual Meeting of Japan Society of Gene Therapy.
  • Place of Presentation: Tochigi
  • Year and Date: 2010-07-01
• [Presentation] AAV Vector Mediated Enzyme Replacement Therapy of Hypophosphatasia (HPP) Model Mice. (2010)
  • Author(s): Matsumoto, T.
  • Organizer: 13th Annual Meeting of the American Society of Gene & Cell Therapy.
  • Place of Presentation: Washington, DC
  • Year and Date: 2010-05-22
• [Presentation] Muscle directed systemic cancer gene therapy for lymphoma using type 8 AAV vector expressing mda-7/IL24. (2010)
  • Author(s): Wang, N.
  • Organizer: 13th Annual Meeting of the American Society of Gene & Cell Therapy.
  • Place of Presentation: Washington, DC
  • Year and Date: 2010-05-21
• [Presentation] TNSALP変異が同定された周産期型低フォスファターゼ症の1例 (2010)
  • Author(s): 大森意索
  • Organizer: 第33回日本小児遺伝学会学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-22
• [Presentation] Genotype frequency of 1559T deletion (1559delT) in the TNSALP gene and clinical significance of hypophoshatasia in Japan. (2010)
  • Author(s): Watanabe A, Naing BT, Sawai H, Karasugi T, Kondo H, Ikegawa S, Orimo H, Shimada T.
  • Organizer: 2010 ACMG Annual Clinical Genetics Meeting.
  • Place of Presentation: Albuquerque, NM
• [Presentation] Long term correction of biochemical and neurological abnormalities of MLD model mice by systemic neonatal injection of serotype 9. (2010)
  • Author(s): Miyake N, Miyake K, Asakawa N, Yamamoto M, Shimada T.
  • Organizer: 13th Annual Meeting of the American Society of Gene & Cell Therapy.
  • Place of Presentation: Washington, DC
• [Presentation] AAV Vector Mediated Enzyme Replacement Therapy of Hypophosphatasia (HPP) Model Mice. (2010)
  • Author(s): Matsumoto T, Yamamoto S, Orimo H, Miyake K, Miyake N, Narisawa S, Millan JL, Fukunaga Y, Shimada T.
  • Organizer: 13th Annual Meeting of the AmericanSociety of Gene & Cell Therapy.
  • Place of Presentation: Washington, DC
• [Presentation] Global gene transfer in the CNS and phenotypic correction of MLD model mice by systemic neonatal injection of serotype 9 AAV vector. (2010)
  • Author(s): Miyake N, Miyake K, Asakawa N, Okabe M, Yamamoto M, Shimada T.
  • Organizer: European Human Genetics Conference 2010.
  • Place of Presentation: Gothenburg, Sweden
• [Presentation] Systemic injection of AAV type 9 in utero facilitates global gene expression in the CNS. (2010)
  • Author(s): Sugano H, Miyake N, Endo A , Miyake K , Shimada T.
  • Organizer: 18th European Society of Gene and Cell Therapy Annual Congress.
  • Place of Presentation: Milano,Italy
• [Presentation] Systemic injection of AAV type 9 in utero facilitates global gene expression in the CNS. (2010)
  • Author(s): Sugano H, Miyake N, Endo A , Miyake K , Shimada T.
  • Organizer: International workshop of lysosomal storage disease.
  • Place of Presentation: Prague, Czech
• [Presentation] Nonsense mutations of COL3A1 gene causing nonsense-mediated mRNA decay in two Japanese patients with Vascular type of Ehlers-Danlos Syndrome. (2010)
  • Author(s): Naing, BT.
  • Organizer: 60th Annual meeting of American Society of Human Genetics ASHG.
  • Place of Presentation: Washington DC
• [Presentation] Gene therapy of adult MLD model mice by intrathecal administration of type 9 AAV vector.
  • Author(s): Miyake, N.
  • Organizer: 15th Annual Meeting of the American Society of Gene & CellTherapy.
  • Place of Presentation: Philadelphia,Pennsylvania
• [Presentation] Gene therapy for lethal murine hyopophosphatasia.
  • Author(s): Shimada T.
  • Organizer: 6th International Alkaline Phosphatase And Hypophosphatasia Symposium.
  • Place of Presentation: Huningue,Alsace,France
  • Invited
• [Presentation] A novel gene therapy strategy for vascular Ehlers-Danlos syndrome.
  • Author(s): Watanabe A.
  • Organizer: First International symposium on Ehlers-Danlos syndrome Ghent Belgium.
  • Place of Presentation: Ghent,Belgium
• [Presentation] Hypermobility Syndrome in Japan.
  • Author(s): Watanabe A.
  • Organizer: First International symposium on Ehlers-Danlos syndrome Ghent Belgium.
  • Place of Presentation: Ghent,Belgium
• [Presentation] AAV9 mediated gene therapy of MLD model mice.
  • Author(s): Miyake, N.
  • Organizer: 20th Annual Meeting of the European Society of Gene & CellTherapy.
  • Place of Presentation: Versailles,France
• [Presentation] Gene Therapy in Japan -Problems and Prospects-
  • Author(s): Shimada, T.
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] Successful treatment of adult MLD model mice by intrathecal administration of AAV9 vector.
  • Author(s): Miyake, N.
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
• [Presentation] 遺伝子治療の最近の動向－ゲノム医療の世界の動向と本邦における臨床応用の展望－.
  • Author(s): 島田 隆
  • Organizer: 第21回日本Cell Death学会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 遺伝子治療の最近の動向－我が国の遺伝子治療臨床研究の進歩－.
  • Author(s): 島田 隆
  • Organizer: つくばオンコロジーフォーラム
  • Place of Presentation: 筑波
  • Invited
• [Presentation] AAV Vector Mediated Gene Therapy for Lysosomal Storage Diseases.
  • Author(s): Shimada, T.
  • Organizer: 第4回国際ライソゾーム病フォーラム・第17回日本ライソゾーム病研究会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Gene therapy of adult MLD model mice by intrathecal administration of type 9 AAV vector.
  • Author(s): Miyake, N.
  • Organizer: 第4回国際ライソゾーム病フォーラム・第17回日本ライソゾーム病研究会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 国内外の遺伝子治療臨床研究に関する審査体制の違いについて.
  • Author(s): 島田 隆
  • Organizer: 第3回国際協力遺伝病遺伝子治療フォーラム
  • Place of Presentation: 東京
  • Invited
• [Book] Development of muscle directed systemic cancer gene therapy. (2013)
  • Author(s): Miyake, K., Shimada, T.
  • Publisher: GeneTherapy/Book 1 (Edited by MingWei) InTech.
• [Book] Prenatal diagnosis of severe perinatal (lethal) hypophosphatasia. (2012)
  • Author(s): Watanabe, A., Orimo, H., Takeshita, T., Shimada, T.
  • Publisher: Prenatal Diagnosis - Morphology Scan and Invasive Methods (Edited by Richard Choy) InTech.
• [Book] Development and application of HIVvectors pseudotyped with HIV envelopes. (2011)
  • Author(s): Miyake, K., Shimada, T.
  • Publisher: Viral Gene Therapy (Edited by Ke Xu)