Gene therapy for vascular stenosis using replieation-competent HSV vector

球囊血管成形术对动脉粥样硬化引起的血管狭窄具有有效作用，特别是在冠状动脉和颈动脉中。然而，这种治疗后再狭窄的发生率为30%至50%，并且没有有效的治疗方法。为了克服这种发病机制，我们构建了细胞特异性的，复制能力的单纯疱疹病毒（HSV）载体，d12.CALP。在该载体中，即早基因ICP 4在平滑肌细胞特异性蛋白钙调蛋白启动子的控制下进行调节。同源重组在病毒胸苷激酶位点进行，因此d12.CALP。显示分裂的钙调蛋白表达细胞，如平滑肌瘤特异性复制。（Cancer Res.61：3969-3977，2001）我们将应用该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。

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.