Clinical development of angiogenesis-induced siRNA for ischemic diseases

在此之前，我们发现了缺氧诱导因子2 α（HIF 2 α）的结合蛋白Int 6/eIF 3e。即使在常氧条件下，Int 6也可作为负反馈因子诱导HIF 2 α的降解。为了进一步研究HIF 2 α的功能，我们设计了siRNA并将其诱导到小鼠皮内空间。siRNA的注射清楚地显示了动脉和静脉的正常血管生成。此外，我们将siRNA注射到猪和大鼠的缺血心脏、小鼠的缺血脑和小鼠的损伤皮肤中。这些实验证明了从局部缺血性损伤和损伤中的明显恢复。为了分析其机制，我们试图使条件性KO小鼠靶向Int 6基因。然而，经过多次筛选，我们仍未能获得良好的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.