Skip Navigation


Nucleic Acids Research Advance Access first published online on December 20, 2006
This version published online on February 1, 2007
Nucleic Acids Research, doi:10.1093/nar/gkl860
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (2570K) Freely available
Right arrow Screen PDF (2573K) Freely available
Right arrowOA All Versions of this Article:
35/3/728    most recent
gkl860v2
gkl860v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Bello-Roufaï, M.
Right arrow Articles by Pitard, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bello-Roufaï, M.
Right arrow Articles by Pitard, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Relationships between the physicochemical properties of an amphiphilic triblock copolymers/DNA complexes and their intramuscular transfection efficiency

Mahajoub Bello-Roufaï1,*, Olivier Lambert2 and Bruno Pitard1

1L'Institut du Thorax, INSERM U533, Faculté de Médecine 44000 Nantes, France and 2IECB-UBS UMR CNRS 5471, Université de Bordeaux 1 33405 Talence, France

*To whom correspondence should be addressed. Tel: +33 2 40 41 29 74; Fax: +33 2 40 41 29 50; Email: bellomb{at}medicine.ufl.edu

Received August 11, 2006. Revised September 25, 2006. Accepted October 3, 2006.

Poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) triblock copolymer (PEO-PPO-PEO) based plasmid delivery systems are increasingly drawing attention in the field of nonviral gene transfer because of their proven in vivo transfection capability. They result from the simple association of DNA molecules with uncharged polymers. We examined the physicochemical properties of PEO-PPO-PEO/DNA mixtures, in which the PEO-PPO-PEO is Lutrol® (PEO75-PPO30-PEO75), formulated under various conditions. We found that interactions between PEO-PPO-PEO and DNA are mediated by the central hydrophobic block within the block copolymer. Dynamic light scattering and cryo-electron microscopy showed that the mean diameter of transfecting particles as well as their stability depended on the PEO-PPO-PEO/DNA ratio and on the ionic composition of the formulating medium. The most active formulation promoting a good tissue-distribution and an optimal transfection was characterized by a reduced electrophoretic mobility, a mean hydrodynamic diameter of ~250–300 nm and by a conserved B-DNA form as shown by circular dichroism studies. Our study also revealed that the stability of these formulations strongly depended on a concentration balance between the DNA and the PEO-PPO-PEO, over which the DNA conformation was modified, micron-sized particles were generated, and the transgene expression was declined. We showed that the physicochemical properties of PEO-PPO-PEO/DNA formulations directly impact the level of gene expression in transfected muscles.

The corresponding author has been changed in this version


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.