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.
Core B: Cell Morphology Core The Cell Morphology Core is an essential component of this grant which aims at gene therapy for homozygous familial hypercholesterolemia (hoFH) and familial LCAT deficiency (FLD) with broader implications for other cardiovascular diseases and liver-directed gene therapy. Successful treatment strategies for these genetic diseases will therefore be of general importance for the public health goals of NHLBI. The Cell Morphology Core will support all three projects of this grant and will be responsible for animal necropsies and tissue processing for histopathology which are essential for the proposed safety studies, for efficacy studies for FLD which will require histopathology, and for nonhuman primate necropsies in the context of isolating neutralizing antibodies from rhesus monkeys.
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