Titre

equipe COSM
chimie organique
santé et matériaux

Phosphorus, Lipids and Vectorization

Thematic members of the Phopshorus, Lipids and Vectorization group (January 2016)

left to right: Charlotte Sevrain (ATER), Olivier Lozach (IE), Hélène Couthon (MCF), Wilfried Berthe (IE), Mélissa Roger (IR), Sylvie Hernot (AI), Laure Deschamps (MCF), Mathieu Berchel (MCF), Thierno Diallo (Master 1), Paul-Alain Jaffrès (Pr.)

 

New amphiphiles as carriers for nucleic acid delivery.

Gene therapy is a new approach in the treatment of inherited or acquired disease. Cationic lipids constitute one class of synthetic vector that can be used to deliver (in vitro or in vivo) nucleic acid such as pDNA and RNA. Our research group is engaged in the synthesis of new phosphorus-based amphiphilic compounds. These amphiphilic compounds can be formulated as a liposomal solution in water and can interact with nucleic acid leading to compact and protect them. These supramolecular aggregates (lipoplexes) have then the physicochemical properties to cross the cell membranes (plasma membrane) to deliver the nucleic acids into cells. Some of our synthetic vectors are efficient to deliver pDNA for in vitro and in vivo assays. Recent results have shown that some of our cationic amphiphiles that have the capacity to transfect eukaryotic cells have also outstanding bactericidal properties. Our work is also dedicated to the development of efficient synthetic protocols to produce new amphiphilic compounds. For this purpose, we used click reactions (Beil. J. Org. Chem., 2014) to produce functionalized amphiphiles (fluorescent lipids).

 

 

         

 Selected Publications


Cationic dialkylarylphosphates: new family of bio-inspired cationic lipids for gene delivery.
S. S. Le Corre, N. Belmadi, M. Berchel, T. Le Gall, J.P. Haelters, P. Lehn, T. Montier, P.A. Jaffrès
Org. Biomol. Chem., 2015, 13, 1122-1132, DOI: 10.1039/c4ob01770f.

Cationic lipophosphoramidates with two different lipid chains: synthesis and evaluation as gene carriers.
Le Corre, S.S. ; Berchel, M. ; Belmadi, N. ; Denis, C. ; Haelters, J.P. ; Le Gall, T. ; Lehn, P. ; Montier, T. ; Jaffrès, P.A.
Org. Biomol. Chem., 2014, 12, 1463-1474, DOI: 10.1039/c3ob42270d.

Arsonium-containing Lipophosphoramides, Poly-functional Nano-carriers for Simultaneous Antibacterial Action and Eukaryotic Cell Transfection
Le Gall, T.; Berchel, M.; Le Hir, S.; Fraix, A.; Salaün, J.Y.; Férec, C.; Lehn, P.; Jaffrès, P.A.; Montier, T.
Adv. Healthcare Mater, 2013, 2, 1513-1524, DOI: 10.1002/adhm.201200478.

The gene transfection properties of a lipophosphoramidate derivative with two phytanyl chains
Lindberg, M.; Carmoy, N. ; Le Gall, T.; Fraix, A.; Berchel, M. ; Lorilleux, C.; Couthon-Gourvès, H. ; Bellaud, P. ; Fautrel, A. ; Jaffrès, P.A.; Lehn, P.; Montier, T.
Biomaterials, 2012, 33, 6240-6253, DOI: 10.1016/j.biomaterials.2012.05.014.

Enhancement of dendritic cells transfection in vivo and of vaccination against B16F10 melanoma with mannosylated histidylated lipopolyplexes loaded with tumor antigen messenger RNA.
Perche, F. ; Benvegnu, T.; Berchel, M. ; Lebegue, L. ; Pichon, C. ; Jaffrès, P.A. ; Midoux P.
Nanomedicine: NBM, 2011, 7, 445-453, DOI: 10.1016/j.nano.2010.12.010.

A novel cationic lipophosphoramidate with di-unsaturated lipid chains : synthesis, physico-chemical and transfection activities.
Le Gall, T. ; Loizeau, D. ; Picquet, E. ; Carmoy, N. ; Yaouanc, J.J. ; Deschamps, L. ; Delépine, P. ; Giamarchi, P. ; Jaffrès, P.A. ; Lehn, P. ; Montier T.
J. Med. Chem. 2010, 53, 1496-1508, DOI: 10.1021/jm900897a.
 

Selected Reviews

Atherton-Todd Reaction: Mechanism, Scope, and Applications.
Le Corre, S.S. ; Berchel, M. ; Couthon-Gourvès, H. ; Haelters, J.P. ; Jaffrès, P.A.
Beilstein J. Org. Chem. (article on invitation), 2014, 10, 1166-1196, DOI: 10.3762/bjoc.10.117.

Lipophosphonate/lipophosphoramidates: a family of synthetic vectors efficient for gene delivery.
M. Berchel, T. Le Gall, H. Couthon-Gourvès, J.-P. Haelters, T. Montier, P. Midoux, P. Lehn, P.-A. Jaffrès.
Biochimie, 2012, 94, 33-41, DOI: 10.1016/j.biochi.2011.07.026.

Chemical vectors for gene delivery: A Current Review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers.
Midoux, P.; Pichon, C. ; Yaouanc, J.J ; Jaffrès, P.A.
Br. J. Pharmacol. 2009, 157, 166-178. (review), DOI: 10.1111/j.1476-5381.2009.00288.x. 

"Progress in cationic lipid-mediated gene transfection: a series of bio-inspired lipids as an example"
Montier, T. ; Benvegnu, T. ; Jaffrès, P.A.; Yaouanc, J.J.; Lehn, P.
Curr. Gene Ther., 2008, 8, 296-312. (Review), DOI: 10.2174/156652308786070989.
  

External Collaborations

  

Pr. T. Montier, Pr. P. Lehn, Dr. T. Le Gall, U INSERM U 1078 – Brest.


  

Dr. P. Midoux, Pr. C. Pichon, CNRS UPR 4301 – Orléans.


 

Dr. B. Pitard, Inserm UMR 1087/CNRS UMR 6291 - Nantes.


 

Pr. T. Benvegnu, ENSCR, UMR CNRS 6226, Rennes 


 

 Pr. P. Guéguan, UMR7610 – Paris.

 Funding

                             

Platform

The SynNanoVect platform, in which we are involved, offers different kits for the vectorisation of nucleic acid and offers expertise for the development of specially designed vectorisation systems. This platform possesses the national label IBISA and is certificated regarding the quality management (ISO 9001).

 

Contact Thématique

Thématique: Phosphore, Lipides et Vectorisation

 Prof. Paul-Alain Jaffrès

UMR-CNRS 6521
 Université de Bretagne Occidentale
6, avenue Victor le Gorgeu.
29238 BREST Cedex 3

Tel : (00 33) (0)2 98 01 61 53
Fax : (00 33) (0)2 98 01 70 01
e-mail : pjaffres@univ-brest.fr