Clinical development of angiogenesis-induced siRNA for ischemic diseases

此前，我们发现了缺氧诱导因子2 α (HIF2alpha)的结合蛋白Int6/eIF3e。即使在常氧条件下，Int6作为负反馈因子诱导hif2 α的降解。为了进一步研究hif2 - α的功能，我们指定siRNA并将其诱导到小鼠皮内空间。注射siRNA可清晰显示动脉、静脉血管生成正常。此外，我们还将siRNA注射到猪和大鼠的缺血心脏、小鼠的缺血大脑和小鼠的损伤皮肤中。这些实验证明了缺血性损伤和损伤的明显恢复。为了分析其作用机制，我们尝试制造条件KO小鼠来靶向Int6基因。然而，经过多次筛选，我们无法获得良好的ES细胞。我们现在进行靶向载体的再克隆，并再次尝试制造KO小鼠。

Previously, we found the binding protein Int6/eIF3e fro hypoxia inducible factor 2 alpha (HIF2alpha). The Int6 works as a negative feedback factor to induce degaradation of HIF2alpha even under normoxia. To further investigation of HIF2alpha function, we designated the siRNA and induce it into mouse intradermal space. The injection of siRNA clearly showed the normal angiogenesis of arteries and veins. In addition, we injected the siRNA into ischemic hearts of pigs and rats, ischemic brains of mouse, and injured skin of mice. these experiments demonstrated the clear recovery from ischemic damage and injury. To analyse the mechanisms, we tried to make conditional KO mice to target the Int6 gene. However, we could not the good ES cells after several screening. we now perform recloning of targeting vectors and try again to make the KO mice.