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Abstract
Schizophrenia (SCZ) is a complex neuropsychiatric disorder thought to arise from an interplay of environmental and genetic risk factors. The presentation of disease symptomology is heterogenous due to the polygenicity of the disorder. The standard antipsychotic drug treatments lack target specificity, have severe side effects, and do not alleviate the most disabling negative and cognitive symptoms. This may be due to a lack of understanding SCZ pathophysiology. Genome-wide association studies (GWAS) identified candidate alleles, largely involved in regulating synaptic function, which confer increased risk for SCZ. The host gene MIR137, contains the primary transcript of microRNA137 (miR137), is strongly implicated in SCZ risk and is associated with more severe psychiatric symptoms. MiR137 regulates tens to hundreds of target transcripts involved in neurodevelopment and synaptic function. Since SCZ is a neurodevelopmental disorder characterized by synaptic dysfunction, miR137 represents an interesting target to modulate protein expression in the prefrontal cortex (PFC), one of the most impacted brain regions. Thus, to improve treatments for people with SCZ, this dissertation investigated the ability of nanoparticles to deliver nucleic acid cargo to the PFC to alter synaptic protein expression.