超级酶基因治疗在阴茎康复中的应用研究：亚型的选择及载体的优化

性功能障碍(ED)是前列腺癌根治术后常见的并发症。虽然阴茎康复（PR）的概念已被临床工作者广为接受，但目前常用的PR方法仍存在疗效欠佳、费用高、使用不方便和患者依从性差等亟待解决的问题。前列环素(PGI2)是诱导平滑肌松弛最主要的血管保护剂。外源性给予PGE2（PGI2的替代物。PGI2极不稳定，不能直接给药）效果显著但有给药不方便，花费大及明显副作用等缺点。我们研究发现：超级酶基因治疗能在阴茎组织内持续性、特异性、靶向性的产生PGI2，促进PR。因此，本项目在前期研究基础上，提出了优化超级酶基因治疗用于PR的新方法：围绕"超级酶中哪种亚型的环氧化酶疗效更佳"，"腺病毒和脂肪干细胞，哪个更适合作为超级酶的载体"，"能否在猕猴上初步验证超级酶基因治疗的安全性和有效性"等疑问进行一系列应用基础研究，力争建立一种优化的阴茎康复新方案。并有望利用此研究结果，开发出一个靶向治疗ED的新方法。

Erectile dysfunction (ED) after radical prostatectomy is an almost unavoidable complication. At present, erectile function recovery rates are widely disparate even in the era of early penile rehabilitation with the scheduled therapy (phosphodiesterase type 5 inhibitors, intracavernosal injection, intraurethral suppository, vacuum erectile device, or combination therapy). Prostacyclin (PGI2), one of the prostanoids, is the main vasoproctector which induc smooth muscle relaxation. PGE2，PGI2 replacement therapy (PGI2 is not used for replacement therapy because it is very unstable), is effective in PR, but at great expense and significant inconvenience. SuperEnzyme,which is capable of continuously, specificity, targetedly producing and releasing PGI2, was created & applied to PR in rats by our group.Our preliminary data show SuperEnzyme gene therapy improve PR in the animal experiments. To further understand the role of SuperEnzyme gene therapy in PR,the following specific aims are proposed:(1)determine which subtype of SuperEnzyme (COX1-10aa-PGIS or COX2-10-aa-PGIS) is better in PR;(2)optimize the carrier of the SuperEnzyem gene therapy(adipose tissue-derivative stem cells or adenovirus); (3)explore the safety and efficacy of the SuperEnzyem gene therapy in monkeys. The answer to the above aims will provide us with novel insight of the SuperEnzyme in PR, which will help us to formulate a new PR regimen. It may also provide prevention strategies & new therapies for other ED.