Project Grant R01OD036239

ENHANCING RIGOR AND REPRODUCIBILITY OF TRANSLATIONAL NONHUMAN PRIMATE MODELS FOR GENETIC AND REGENERATIVE THERAPIES - THIS APPLICATION IS SUBMITTED IN RESPONSE TO PAR-23-040 WITH THE GOAL OF INTEGRATING CUTTING-EDGE IN VIVO IMAGING TECHNOLOGIES AND KEY IMMUNOLOGIC ASSESSMENTS TO ENHANCE THE RIGOR AND REPRODUCIBILITY OF TRANSLATIONAL NONHUMAN PRIMATE MODELS FOR GENETIC AND REGENERATIVE THERAPIES. THE PROPOSAL MEETS THE OBJECTIVE OF PAR-23-040, WHICH IS FOCUSED ON "...DEVELOPING AND IMPLEMENTING BROADLY APPLICABLE TECHNOLOGIES, TOOLS, AND RESOURCES FOR...ENHANCING RIGOR, REPRODUCIBILITY, AND TRANSLATABILITY OF ANIMAL RESEARCH". WE WILL SUPPORT TRANSLATIONAL RESEARCH BY INCORPORATING TOTAL-BODY POSITRON EMISSION TOMOGRAPHY (PET) AND CORRELATIVE ASSESSMENTS OF THE IMMUNE SYSTEM. THE INVESTIGATIONS PROPOSED WILL ENHANCE THE RHESUS MONKEY MODEL SYSTEM BY CREATING OR IMPROVING STUDY PROTOCOLS THAT PROVIDE A HIGH LEVEL OF SENSITIVITY AND REPRODUCIBILITY FOR ASSESSMENTS THAT ARE IMPORTANT TO CLINICAL TRANSLATION. THE SPECIFIC AIMS ARE: (1) USE TOTAL-BODY PET IMAGING TO LONGITUDINALLY MONITOR GENE TRANSFER AND BIODISTRIBUTION IN PRECLINICAL STUDIES OF FETAL OR JUVENILE RHESUS MONKEYS FOR CLINICAL TRANSLATION, AND (2) EXPLORE NEW READOUTS OF IMMUNE RESPONSES TO INNOVATIVE THERAPEUTICS IN TISSUE SITES USING T-CELL TRACKING IN TRANSLATIONAL NONHUMAN PRIMATE STUDIES. THESE INVESTIGATIONS WILL ADDRESS RELATIONSHIPS BETWEEN LOCAL T-CELL INFILTRATION AND CIRCULATING IMMUNOPHENOTYPES WITH CORRELATIVE IN VIVO IMAGING, WHICH WILL ENHANCE MODELS AND PROVIDE NEW METHODS TO ASSESS THE PRIMATE IMMUNE SYSTEM. MONITORING INFLAMMATION AND IMMUNITY IN TARGETED AND NON-TARGETED TISSUES IS CRITICALLY IMPORTANT TO ENSURE SAFETY AS NEW THERAPEUTICS TRANSITION TO THE CLINIC FOR A RANGE OF COMMON AND RARE DISEASES. THESE STUDIES WILL PROVIDE PREDICTIVE PROTOCOLS AND TOOLS WHICH WILL INFORM PRECLINICAL AND IND- ENABLING STUDIES FOR FUTURE HUMAN APPLICATIONS ACROSS AGE GROUPS.