The Immune Function Studies Core (Core C) is designed to support the proposed studies of yc Foamy Virus gene therapy for SCID-Xl that will ufilize in vitro testing in cell lines as well as in vivo testing using pre- clinical animal models. The Core will support all three projects (1, 2, and 3) of this Program Project Grant and is focused primarily on evaluation of funcfional immune recovery after gene therapy in this severe immunodeficiency disorder. The Core will perform mulfi-parameter flow cytometry analyses of human, mouse, and canine cells to measure viral marking and immune reconstitution after yc FV gene therapy. In addifion. Core C will evaluate restoration of specific functional deficits (for example restoration of lL-2 signaling) in yc FV treated cells and will work with the SCRl Immunology Diagnosfic Laboratory (IDL) to analyze funcfional immune responses to neoanfigen (bacteriophage OX174) vaccinafion in treated dogs. Flow cytometry and gene sequencing will be performed by the Core to rapidly identify affected SCID-Xl dogs shortly after birth. Core C personnel will direcfiy assist project investigators in the analysis and interpretation of data generated by the Core. Data from these analyses will be used to evaluate which yc FV vector is most efficacious and which conditioning regimen facilitates the most complete immune recovery.

Public Health Relevance

Immune dysfuncfion and susceptibility to severe, life-threatening infections are the hallmarks of the fatal childhood immunodeficiency disorder, SCID-Xl. Evaluafion of immune reconstitufion and recovery of functional immune responses after potenfially curative gene therapy is therefore vital for judging whether a particular treatment is efficacious. Core C will evaluate immune recovery in this trial of Foamy Viral mediated gene therapy for SCID-Xl.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-JTS-I (S1))
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Seattle Children's Hospital
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