Nucleic Acids Research, Vol 27, Issue 17 3510-3517, Copyright © 1999 by Oxford University Press
MC Morris, L Chaloin, J Mery, F Heitz and G Divita
We have shown previously that a peptide, MPG, derived from the hydrophobic
fusion peptide of HIV-1 gp41 and the hydrophilic nuclear localisation
sequence of SV40 large T antigen, can be used as a powerful tool for the
delivery of oligonucleotides into cultured cells. Now we extend the
potential of MPG to the delivery of nucleic acids into cultured cells. In
vitro, MPG interacts strongly with nucleic acids, most likely forming a
peptide cage around them, which stabilises and protects them from
degradation in cell culture media. MPG is non- cytotoxic, insensitive to
serum and efficiently delivers plasmids into several different cell lines
in only 1 h. Moreover, MPG enables complete expression of the gene products
encoded by the plasmids it delivers into cultured cells. Finally, we have
investigated the potential of MPG as an efficient delivery agent for gene
therapy, by attempting to deliver antisense nucleic acids targeting an
essential cell cycle gene. MPG efficiently delivered a plasmid expressing
the full-length antisense cDNA of human cdc25C, which consequently
successfully reduced cdc25C expression levels and promoted a block to cell
cycle progression. Based on our results, we conclude that MPG is a potent
delivery agent for the generalised delivery of nucleic acids as well as of
oligonucleotides into cultured cells and believe that its contribution to
the development of new gene therapy strategies could be of prime interest.
ARTICLES
A novel potent strategy for gene delivery using a single peptide vector as a carrier
Centre de Recherches de Biochimie Macromoleculaire, UPR-1086 CNRS, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.
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