Optimisation of dendrimer-mediated gene transfer by anionic oligomers.
BACKGROUND
The application of synthetic vectors for gene transfer has potential advantages over virus-based systems. Their use, however, is limited since they generally lack the efficiency of gene transfer achieved with recombinant viral vectors such as adenovirus. Polyamidoamine (PAMAM) and phosphorus-containing dendrimers (P-dendrimers) are specific polymers with a defined spherical structure. They bind to DNA through electrostatic interactions thus forming complexes that efficiently transfect cells in vitro.


RESULTS
The influence of anionic oligomers (oligonucleotides, dextran sulfate) on dendrimer-mediated polyfection of cultured cells has been studied. Anionic oligomers have been found to increase significantly the capacity of the PAMAM and P-dendrimers for DNA delivery into cells when they were mixed with plasmid DNA before addition of dendrimers. The efficiency of the DNA/dendrimer penetration depends on the size, structure and charge of anionic oligomers.


CONCLUSIONS
Our results represent an important step towards the optimisation of gene transfer mediated by two types of dendrimers. The use of anionic oligomers improves the efficiency of gene expression within cells. As a consequence, a very efficient cell polyfection can be achieved with a lower plasmid quantity for the PAMAM dendrimer greatly increasing the gene expression level for P-dendrimers.
Maksimenko
Andrei V
AV
BioAlliance Pharma SA, 59 boulevard du Général Martial Valin, 75015 Paris, France. andremak@igr.fr
Mandrouguine
Vasilii
V
Gottikh
Marina B
MB
Bertrand
Jean-Remi
JR
Majoral
Jean-Pierre
JP
Malvy
Claude
C
D016475:3T3 Cells; D000818:Animals; D004247:DNA / Q000378:metabolism; D050091:Dendrimers; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009841:Oligonucleotides / Q000378:metabolism; D011073:Polyamines
D050091:Dendrimers; D009841:Oligonucleotides; C104700:PAMAM Starburst; D011073:Polyamines; D004247:DNA