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Explorations of high-intensity therapeutic ultrasound and microbubble-mediated gene delivery in mouse liver

Gene Therapy volume 18, pages 1006–1014 (2011)Cite this article

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Abstract

Ultrasound (US) combined with microbubbles (MBs) is a promising technology for non-viral gene delivery. Significant enhancements of gene expression have been obtained in our previous studies. To optimize and prepare for application to larger animal models, the luciferase reporter gene transfer efficacy of lipid-based Definity MBs of various concentrations, pressure amplitudes and a novel unfocused high-intensity therapeutic US (HITU) system were explored. Luciferase expression exhibited a dependence on MB dose over the range of 0–25 vol%, and a strong dependence on acoustic peak negative pressure at over the range of 0–3.2 MPa. Gene expression reached an apparent plateau at MB concentration ⩾2.5 vol% or at negative pressures >1.8 MPa. Maximum gene expression in treated animals was 700-fold greater than in negative controls. Pulse train US exposure protocols produced an upward trend of gene expression with increasing quiescent time. The hyperbolic correlation of gene expression and transaminase levels suggested that an optimum gene delivery effect can be achieved by maximizing acoustic cavitation-induced enhancement of DNA uptake and minimizing unproductive tissue damage. This study validated the new HITU system equipped with an unfocused transducer with a larger footprint capable of scanning large tissue areas to effectively enhance gene transfer efficiencies.

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Acknowledgements

This work was supported by R01 (R01 HL69049) and R21 (R21 HL089038) Grants from NIH-NHLBI.

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Authors and Affiliations

  1. Department of Pediatrics, Seattle Children's Research Institute, University of Washington, Seattle, WA, USA

    S Song, Z Shen, L Chen & C H Miao

  2. Applied Physics Laboratory, Center for Industrial and Medical Ultrasound, University of Washington, Seattle, WA, USA

    A A Brayman & C H Miao

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  1. S Song
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  2. Z Shen
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  3. L Chen
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Correspondence to C H Miao.

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Song, S., Shen, Z., Chen, L. et al. Explorations of high-intensity therapeutic ultrasound and microbubble-mediated gene delivery in mouse liver. Gene Ther 18, 1006–1014 (2011). https://doi.org/10.1038/gt.2011.34

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