We will investigate whether focused ultrasound (FUS) can increase delivery to the brain of a non-viral gene vector given by the intranasal route of administration. Aim 1 will examine different FUS treatment conditions to determine if FUS can increase total plasmid DNA nanoparticle (NP) delivery and transgene expression in the sonicated regions, the rat substantia nigra and striatum, two brain areas involved in Parkinson's Disease (PD). Aim 2 will test whether FUS improves tissue penetration and alters cellular transfection patterns in the sonicated regions following intranasal doses of DNA NPs. If successful, FUS may enable agents with poor capabilities of crossing the blood-brain barrier (BBB), e.g. neurotrophic factors, viral and non-viral vectors encoding them, to become disease-altering therapies by a non-invasive route of administration.