BACKGROUND: Although viral vector systems are efficient to transfect foreign genes into blood vessels, safety issues remain in relation to @entity1 gene therapy. In this study, we examined the feasibility of a novel nonviral vector system by using high-frequency, low-intensity ultrasound irradiation for transfection into blood vessels. METHODS AND RESULTS: Luciferase plasmid mixed with or without echo contrast microbubble (Optison) was transfected into cultured @entity1 vascular smooth muscle cells (VSMC) and endothelial cells (EC) with the use of ultrasound. Interestingly, luciferase activity was markedly increased in both cell types treated with Optison. We then transfected luciferase plasmid mixed with Optison by means of therapeutic ultrasound into @entity35 artery. Two days after transfection, luciferase activity was significantly higher in carotid artery transfected with luciferase gene with Optison and ultrasound than with plasmid alone. In addition, we transfected an anti-oncogene ( @entity10740 ) plasmid into carotid artery after @entity130 as a model of gene therapy for @entity256 . Two weeks after transfection, the intimal-to-medial area ratio in @entity35 transfected with wild-type @entity10740 plasmid complexed with Optison by means of ultrasound was significantly decreased as compared with control, accompanied by a significant increase in @entity10740 protein. No apparent @entity137 such as @entity32 could be detected in blood vessels transfected with plasmid DNA with ultrasound and Optison. CONCLUSIONS: Overall, we demonstrated that an ultrasound transfection method with Optison enhanced transfection efficiency of naked plasmid DNA into blood vessels without any apparent @entity137 . Transfection of @entity10740 plasmid with the use of this method should be useful for safe clinical gene therapy without a viral vector system.

Local delivery of plasmid DNA into XXXX carotid artery using ultrasound.

@entity1 :: ('9606', 'Species') :: ['human'] @entity10740 :: ('301300(Tax:10116)', 'Gene') :: ['p53'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity256 :: ('MESH:D023903', 'Disease') :: ['restenosis'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity130 :: ('MESH:D014947', 'Disease') :: ['balloon injury']
@entity35 :: (10116,Species) :: ['rat']
