Gene therapy for vascular stenosis using replieation-competent HSV vector

使用具有复制能力的 HSV 载体进行血管狭窄的基因治疗

• 批准号: 12671353
• 负责人: MIYATAKE Shin-ichi
• 金额: $ 2.18万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671353/
• 关键词: gene therapy; replication-competent virus vector; vascular smooth muscle cells; atherosclrosis; calponin; organ transplantation; gene therapy; smooth muscle cell; re-stenosis; leiomyosarcoma; HSV; cell-specific replication; replication-compete

Balloon angioplasty has a potent role for vascular stenosis due to atherosclerosis, especially in coronary and carotid arteries. However, re-stenosis after this treatment occurred at the rate of 30 to 50 % and there is no effective treatment to this pathogenesis. To overcome this pathogenesis, we constructed cell-specific, replication-competent herpes simplex virus (HSV) vector, d12.CALP. In this vector, immediate early gene, ICP4 is regulated under control of smooth muscle cell-specific protein, calponin, promoter. Homologous recombination was done at the locus of viral thymidine kinase, therefore d12.CALP. showed dividing calponin-expressing cell, such as leiomyosarcoma-specific replication. (Cancer Res. 61:3969-3977, 2001) We will apply this virus for the treatment of arterial stenosis due to atherosclerosis and vascular and organ transplantation.

球囊血管成形术对于动脉粥样硬化引起的血管狭窄具有有效的作用，特别是在冠状动脉和颈动脉中。然而，这种治疗后的再狭窄发生率为30%至50%，并且对于这种发病机制尚无有效的治疗方法。为了克服这种发病机制，我们构建了细胞特异性、具有复制能力的单纯疱疹病毒 (HSV) 载体 d12.CALP。在该载体中，立即早期基因 ICP4 在平滑肌细胞特异性蛋白、钙调蛋白、启动子的控制下受到调节。同源重组是在病毒胸苷激酶位点进行的，因此是 d12.CALP。显示分裂的钙调蛋白表达细胞，如平滑肌肉瘤特异性复制。 (Cancer Res. 61:3969-3977, 2001) 我们将应用这种病毒治疗动脉粥样硬化引起的动脉狭窄以及血管和器官移植。

项目成果

Masao Takagaki, et al.: "Boronated Dipeptide Borotrimethylglycylphenylalanine as a potentialboron carrier in boron neutron capture therapy for malignant brain tumor"Radiat Res.. 156. 118-122 (2001)

Masao Takagaki等人：“硼化二肽硼三甲基甘氨酰苯丙氨酸作为恶性脑肿瘤的硼中子捕获疗法中的潜在硼载体”Radiat Res.. 156. 118-122 (2001)

Yasunori Okubo, et al.: "The time course study of osteoinduction by bone morphogenetic protein-2 via adenoviral vector"Life Sciences. 70. 325-336 (2001)

Yasunori Okubo 等人：“骨形态发生蛋白 2 通过腺病毒载体进行骨诱导的时间过程研究”生命科学。

Shin-Ichi Miyatake: "Gene therapy using Replication-competent HSV vector (in Japanese)"Surgery. (in press).

Shin-Ichi Miyatake：“使用具有复制能力的 HSV 载体进行基因治疗（日语）”手术。

Norihiro Matsuoka, et al.: "Overexpression of bFGF and Bcl-xL with adenoviral vectors protects primarily cultured-neurons against glutamate insult"Neurosurgery. (in press).

Norihiro Matsuoka 等人：“用腺病毒载体过度表达 bFGF 和 Bcl-xL 可保护原代培养神经元免受谷氨酸损伤”神经外科。

Yasunori Okubo, et al.: "In vitro andIn vivo Study of Bone morphogenetic protein-2 Expre ssing Adenoviral Vector"J. Bone Joint Surg. Am.. 83. 99-104 (2001)

Yasunori Okubo 等：“骨形态发生蛋白-2 表达腺病毒载体的体外和体内研究”J。