Cationic microbubbles and antibiotic-free miniplasmid for sustained ultrasound–mediated transgene expression in liver

Despite the increasing number of clinical trials in gene therapy, no ideal methods still allow non-viral gene transfer in deep tissues such as the liver. We were interested in ultrasound (US)-mediated gene delivery to provide long term liver expression. For this purpose, new positively charged micro...

Full description

Saved in:
Bibliographic Details
Published in:Journal of controlled release 2017-09, Vol.262, p.170-181
Main Authors: Manta, Simona, Renault, Gilles, Delalande, Anthony, Couture, Olivier, Lagoutte, Isabelle, Seguin, Johanne, Lager, Franck, Houzé, Pascal, Midoux, Patrick, Bessodes, Michel, Scherman, Daniel, Bureau, Michel-Francis, Marie, Corinne, Pichon, Chantal, Mignet, Nathalie
Format: Article
Language:English
Subjects:
Animals
Biotechnology
Cationic microbubbles
Chemical Sciences
DNA - administration & dosage
Gene Transfer Techniques
HeLa Cells
Humans
Image-guided delivery
Life Sciences
Lipids - chemistry
Liver - diagnostic imaging
Liver - metabolism
Liver gene delivery
Luciferases - genetics
Luciferases - metabolism
Mice, Inbred BALB C
Microbubbles
Miniplasmid
Organic chemistry
Pharmaceutical sciences
Physical delivery
Plasmids
Transfection
Transgenes
Ultrasonic Waves
Ultrasonography
Ultrasound imaging
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Despite the increasing number of clinical trials in gene therapy, no ideal methods still allow non-viral gene transfer in deep tissues such as the liver. We were interested in ultrasound (US)-mediated gene delivery to provide long term liver expression. For this purpose, new positively charged microbubbles were designed and complexed with pFAR4, a highly efficient small length miniplasmid DNA devoid of antibiotic resistance sequence. Sonoporation parameters, such as insonation time, acoustic pressure and duration of plasmid injection were controlled under ultrasound imaging guidance. The optimization of these various parameters was performed by bioluminescence optical imaging of luciferase reporter gene expression in the liver. Mice were injected with 50μg pFAR4-LUC either alone, or complexed with positively charged microbubbles, or co-injected with neutral MicroMarker™ microbubbles, followed by low ultrasound energy application to the liver. Injection of the pFAR4 encoding luciferase alone led to a transient transgene expression that lasted only for two days. The significant luciferase signal obtained with neutral microbubbles decreased over 2days and reached a plateau with a level around 1 log above the signal obtained with pFAR4 alone. With the newly designed positively charged microbubbles, we obtained a much stronger bioluminescence signal which increased over 2days. The 12-fold difference (p
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2017.07.015