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Evaluation of the muscle gene transfer activity of a series of amphiphilic triblock copolymers
Author(s) -
AlimiGuez Debborah,
Leborgne Christian,
Pembouong Gaelle,
Van Wittenberghe Laetitia,
Mignet Nathalie,
Scherman Daniel,
Kichler Antoine
Publication year - 2009
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1396
Subject(s) - poloxamer , in vivo , copolymer , amphiphile , membrane , reporter gene , biophysics , in vitro , transgene , polymer , transfection , chemistry , materials science , polymer chemistry , gene expression , biochemistry , gene , organic chemistry , biology , microbiology and biotechnology
Background Amphiphilic triblock copolymers such as the polyethylene oxide‐polypropylene oxide‐polyethylene oxide L64 (PEO 13 ‐PPO 30 ‐PEO 13 ) significantly increase transgene expression after injection of DNA/polymer mixtures into skeletal muscles. To better understand the way such copolymers act, we studied the behaviour of different poloxamers, including L64, both in vitro and in vivo . Methods The in vitro and in vivo transfection activity of five copolymers that differ either by their molecular weight or by their hydrophilic/hydrophobic balance was evaluated. Furthermore, we also studied the membrane permeabilizing properties of the poloxamers. Results The results obtained indicate that, after intramuscular administration of DNA/poloxamer formulations, all five compounds were able to significantly increase the expression levels of luciferase compared to an injection of naked DNA. Using a LacZ expression cassette, up to 30% of the muscle fibers expressed the reporter gene. Furthermore, we show that the effect can be obtained using different promoters. Finally, we document that, to some extent, all five poloxamers possess membrane permeabilizing properties. Conclusions Taken together, the results obtained in the present study show that there is a large flexibility in terms of molecular weight and EO/PO ratio for obtaining increased levels of transgene expression in vivo . Copyright © 2009 John Wiley & Sons, Ltd.