Gene therapy in golden retriever muscular dystrophy model

金毛猎犬肌营养不良模型的基因治疗 本项目将重点研究DMD犬模型(GRMD)，以研究血管介导的基因传递 AAV向四肢传播，最终进入全身。具体目标1旨在比较区域 四肢动脉和静脉途径的基因传递效率。动脉加压分娩和/或 一些实验室在早期研究中对血管扩张器进行了研究。但最近的研究已经转向 静脉加压给药方式。然而，一份最新的报告再次恢复了动脉法，但 不需要使用任何额外的压力和药物。这些方法各有利弊，但 从来没有并排比较过。在目标1中，我们建议对区域AAV矢量进行比较和优化 狗的四肢给药方法。特定目标2旨在检测系统的基因传递效率 犬的AAV8和AAV9。此前，我们和其他人已经证明，新的AAV血清型可以实现 通过简单静脉注射在小鼠和仓鼠体内进行全身基因传递。在目标2中，我们计划探索 AAV8和AAV9均可用于犬的全身基因传递。我们还将研究任何新的AAV载体 由项目2产生。

Gene therapy in golden retriever muscular dystrophy model This project will focus on the DMD dog model (GRMD) to investigate blood-vessel-mediated gene delivery of AAV vectors into the limbs and eventually the wholedody. Specific Aim 1 is designed to compare regional gene delivery efficiency of arterial and venous methods in the limbs. Arterial delivery with pressure and/or with vessel dilators was investigated in early studies by a few labs. But more recent studies have switched to the pressurized intravenous delivery methods. However, a latest report revived the arterial method again, but without the use of any additional pressure and drugs. These methods have their pros and cons, but are never compared side-by-side. In Aim 1 we propose to compare and optimize the regional AAV vector delivery methods in dog limbs. Specific Aim 2 is designed to examine systemic gene delivery efficiency of AAV8 and AAV9 in dogs. Previously we and others have shown that new serotypes of AAV can achieve wholebody gene delivery by simple intravenous injection in mice and hamsters. In Aim 2, we plan to explore both AAV8 and AAV9 for systemic gene delivery in the dogs. We will also examine any novel AAV vectors yielded by Project 2.