Document Detail


Explorations of high-intensity therapeutic ultrasound and microbubble-mediated gene delivery in mouse liver.
MedLine Citation:
PMID:  21451579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S Song; Z Shen; L Chen; A A Brayman; C H Miao
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-03-31
Journal Detail:
Title:  Gene therapy     Volume:  18     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-13     Completed Date:  2012-01-30     Revised Date:  2012-05-11    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  1006-14     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Seattle Children's Research Institute, University of Washington, Seattle, WA 98101, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Fluorocarbons / therapeutic use
Gene Expression*
Gene Transfer Techniques*
Liver*
Luciferases / metabolism
Mice
Microbubbles / therapeutic use*
Pressure
Transaminases / metabolism
Ultrasonic Therapy / methods*
Grant Support
ID/Acronym/Agency:
R01 HL69049/HL/NHLBI NIH HHS; R21 HL089038/HL/NHLBI NIH HHS; R33 HL089038/HL/NHLBI NIH HHS; R33 HL089038-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Definity; 0/Fluorocarbons; EC 1.13.12.-/Luciferases; EC 2.6.1.-/Transaminases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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