Core B - Cell Morphology Core

摘要 核心B：细胞形态核心 细胞形态学核心将通过提供尸检和组织学来支持这三个项目 服务项目1中LCAT缺乏症基因治疗的药物毒性和疗效研究将严重依赖于 器官收获、一般组织病理学和肾脏病理学，尤其是所有这些均由中心进行。的 Core先前在小鼠和非人灵长类动物中进行了FH基因治疗的安全性研究， 对肾脏组织病理学所需的特殊染色和薄切片技术也有经验。 项目2将开发一种优化的LCAT缺陷小鼠模型，该模型将再次需要肾脏组织学检查。 由核心执行。项目3将选择和研究一种具有高嗜性的NAB逃避型AAV3B变体， 人肝细胞。核心将分析异种移植小鼠肝脏中人细胞的载体向性， 将在小鼠和NHP中测试主要候选人的组织病理学和转基因 表达，并分析异种移植肝脏，该异种移植肝脏用来自接受 表达hLDLR的前导载体。核心还将参与免疫调节实验， 支持NHP尸检并进行组织病理学分析。

ABSTRACT Core B: Cell Morphology Core The Cell Morphology Core will support all three projects of this grant by providing necropsy and histology services. Pharm-tox and efficacy studies in Project 1 for gene therapy of LCAT deficiency will rely heavily on organ harvest, general histopathology and kidney pathology in particular all to be performed by the Core. The Core has previously performed safety studies in mice and nonhuman primates for gene therapy of FH and is also experienced in techniques needed for kidney histopathology such as special stains and thin sectioning. Project 2 will develop an optimized LCAT-deficient mouse model which will again require kidney histology to be performed by the Core. Project 3 will select and study an NAB-evading AAV3B variant with high tropism for human hepatocytes. The Core will analyze vector tropism for human cells in xenograft mouse livers engrafted with human hepatocytes, will test the leading candidates in mice and NHPs for histopathology and transgene expression, and analyze xenograft livers repopulated with human hoFH hepatocytes from mice that received the lead vector expressing hLDLR. The Core will also be involved in the immune modulation experiments by supporting NHP necropsies and performing histopathological analyses.