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Physicochemical Parameters of Non-Viral Vectors that Govern Transfection Efficiency

[ Vol. 8 , Issue. 5 ]


Benoit Barteau, Raphael Chevre, Emilie Letrou-Bonneval, Romain Labas, Olivier Lambert and Bruno Pitard   Pages 313 - 323 ( 11 )


Gene therapy is based on the vectorization of nucleic acids to target cells and their subsequent expression. Cationic lipids and polymers are the most widely used vectors for the delivery of DNA into cultured cells. Nowadays, numerous reagents made of these cationic molecules are commercially available and used by researchers from the academic and industrial field. By contrast their evaluations in preclinical programs have revealed that their use for in vivo applications will be more problematic than their massive use in vitro. This is mostly due to the physicochemical properties of cationic vectors/DNA complexes, which are the result of their mode of interaction. Indeed, these cationic vectors interact through electrostatic forces with negatively charged DNA. This results in the formation of highly organized positively charged supramolecular structures where DNA molecules are condensed. Association of DNA with cationic lipids under a micellar or liposomal form leads to lamellar organization with DNA molecules sandwiched between lipid bilayers. Although the lamellar phase is the common described structure, as evidenced by small-angle X-ray scattering and electron microscopy, some cationic lipid combined with a hexagonal forming lipid could also result with DNA in an inverted hexagonal structure. Despite a lot of effort, the precise mechanism of gene transfer with cationic vector is still ill-defined. Here, our objective was to overview the main relationships between the physico chemical properties of cationic lipid/DNA complexes and their transfection efficiency. An overview of a new class of vectors consisting of amphiphilic block copolymers designed for in vivo delivery is also presented and discussed.


Cationic lipid, cryo-TEM, small-angle X ray scattering, morphology, DNA, Amphiphilic block copolymer


INSERM, U915, 1 Rue Gaston Veil, 44035 Nantes, France.

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