The Immunology Core will function as the central facility for quantifying adaptive cellular and humoral immunity to AAV capsid and encoded transgene proteins in murine and monkey models of vector-mediated gene delivery. This core has two functions. The first is to validate in monkeys the effectiveness of immune suppressive therapy that is designed to prolong transgene expression by blunting host cell-mediated T cell responses. The second objective of the Core is to provide insights into the relationship between immunity and the duration or strength of micro-dystrophin (Project 1), and CT GalNAc transferase (Project 2) gene expression in rAAV-treated mdx mice and rhesus macaques. Specifically we hope to establish whether there is a temporal kinetic relationship between the onset of immunity to the capsid or the transgene encoded CT GalNac or microdystrophin and loss of transgene expression in muscle. Host immune responses to AAV capsid proteins and human transgenes like dystrophin or CT GalNac might influence the longevity of any observed therapeutic effect. Immunity is therefore a potentially critical variable in the pathway forward to human clinical trials. Information on whether immune responses are generated, or alter gene expression in transduced muscle of animals, should help establish safety profiles and predict the potential for success in humans. The Core will monitor anti-AAV NAb and T-cell immune responses (IFNELISpot) for both projects involving mdx mice and monkeys. Transgene-specific antibody responses (ELISA) will also be quantified for both projects.
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