Core B - Cell Morphology Core

摘要 核心B：细胞形态核心 细胞形态核心将通过提供尸检和组织学来支持这笔赠款的所有三个项目 服务。LCAT缺乏症基因治疗项目1中的药物毒性和疗效研究将严重依赖于 器官采集，一般组织病理学，特别是肾脏病理学，都将由核心进行。这个 CORE此前曾在小鼠和非人类灵长类动物身上进行过FH和IS基因治疗的安全性研究 精通肾脏组织病理学所需技术，如特殊染色和薄层切片。 项目2将开发一种优化的LCAT缺陷小鼠模型，这将再次要求肾脏组织学 由核心执行。项目3将选择和研究一个高取向的规避NAB的AAV3B变种 人肝细胞。Core将分析人类细胞在移植的异种小鼠肝脏中的载体取向 对于人类肝细胞，将在小鼠和NHP中测试领先的候选组织病理学和转基因 表达和分析重组人HoFH肝细胞的异种移植肝 表达hLDLR的前导载体。Core还将通过以下方式参与免疫调节实验 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.