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.
Nucleic Acids Research (Impact Factor: 9.11). 10/1999; 27(17):3510-7. DOI: 10.1093/nar/27.17.3510
Source: PubMed
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.


Available from: May C Morris