Background: The common marmoset (Callithrix jacchus) could provide an appropriate model for neuromuscular diseases because of its higher brain function and physiological resemblance to human. Although production of transgenic marmosets from zygote transduced with lentiviral vector were reported, this strategy is too costly and not efficient with various reasons. In contrast, an adeno-associated virus vector (rAAV) has great advantages to induce pathology in the aged animals. However, fully maturated blood-brain interface (BBI) significantly limits passive rAAV transport from circulation to the brain. To overcome this issue, we investigated BBI opening, which is a promising technology to make cerebral capillary open by transiently disrupting tight junction in BBI with ultrasound irradiation (UI) just after i.v. injection of microbubble (MB).Methods: Commercially available MB or homemade bubbleliposome (BL) mixed with evans blue were i.v. injected into the femoral vein of the anesthetized adult marmosets. rAAV1 was also injected simultanously in certain trials. Subsequently, transcranial (TC) UI to the brain was performed for several minutes. The brain was removed 24 hrs after the UI. To visualize the leakage of albumin (ALB) in more detail, cryosections were immunologically stained with antibodies against ALB and CD31. Thin coronal slice of the brain was pieced into various parts, and genome DNA was extracted from the each pieces. Then relative rAAV genome copies were measured by qPCR. For live imaging analysis, BL mixed with carbon 11-labeled aminoisobutyric acid were i.v. injected into the tail vein. Subsequently, TCUI and positron emission tomography (PET) scan were performed.Results: In TCUI from the temporal region, ALB mainly leaked at the temporal cortex and hippocampus. In TCUI from circumference, ALB leakage seemed to occur at whole brain except for white matter.Microscopically, ALB leakage was found around the blood vessels of 10-50 mm in diameter. Especially, leakage in hippocampus was prominent. Relative rAAV genome copies were imbalanced between symmetrical piece pair. PET revealed ALB leakage not only in hippocampus but also in the anterior cingulate cortex, basal ganglia, optic tract, amygdala, and superior temporal gyrus.Conclusion: UI-mediated MB-assisted TC-BBI opening is promising approach in the generation of the disease model based on adult common marmoset.