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Optimisation of dendrimer‐mediated gene transfer by anionic oligomers
Author(s) -
Maksimenko Andrei V.,
Mandrouguine Vasilii,
Gottikh Marina B.,
Bertrand JeanRemi,
Majoral JeanPierre,
Malvy Claude
Publication year - 2003
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.319
Subject(s) - dendrimer , transfection , gene delivery , oligonucleotide , chemistry , dna , biophysics , polymer , dextran , plasmid , combinatorial chemistry , gene , polymer chemistry , biochemistry , organic chemistry , biology
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 . Methods and 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. Copyright © 2002 John Wiley & Sons, Ltd.