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- W1992166802 abstract "Systemic gene transfer using AAV_6 serotype_vectors has been shown to be an efficient route of application in mice. However, systemic application requires high doses of vector or pre_treatment with VEGF to allow vascular permeabilization. The aim of our study was to analyse whether ultrasound_targeted microbubble destruction can augment virus uptake in the heart after intravenous administration. Lipid stabilized microbubbles loaded with 4×10(10) genomic particles of AAV6 encoding for a luciferase reporter gene under the control of a CMV_enhanced 1.5 kb myosin_light chain promoter were infused into the jugular vein of adult (250g) Sprague_Dawley rats. During the infusion high mechanical index ultrasound was administered to the heart. After 4 weeks, organs were harvested and analyzed for reporter gene expression. In contrast to low cardiac expression after systemic transfer of the vector solution without ultrasound, ultrasound_mediated destruction of microbubbles augmented cardiac reporter activities by more than one order of magnitude. Specificity of gene transfer was also increased since background activities in extracardiac organs such as liver and lung were similar with or without ultrasound. In conclusion, ultrasound_targeted microbubble destruction augments cardiac gene transfer with low titer AAV_6 serotype vectors in rats. This approach may be suitable also for increasing efficiency and specificity of AAV_mediated gene transfer in larger species and holds promise for human gene therapy." @default.
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- W1992166802 date "2006-01-01" @default.
- W1992166802 modified "2023-09-26" @default.
- W1992166802 title "236. Ultrasound_Targeted Microbubble Destruction Augments Cardiac AAV_Mediated Gene Transfer after Systemic Administration in Adult Rats" @default.
- W1992166802 doi "https://doi.org/10.1016/j.ymthe.2006.08.262" @default.
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