A novel potent strategy for gene delivery using a single peptide vector asa carrier

We have shown previously that a peptide, MPG, derived from the hydrophobic fusion peptide of HIV-1 gp41 and the hydrophilic nuclear localisation seque nce of SV40 large T antigen, can be used as a powerful tool for the deliver y of oligonucleotides into cultured cells. Now we extend the potential of M PG to the delivery of nucleic acids into cultured cells, In vitro, MPG inte racts strongly with nucleic acids, most likely forming a peptide cage aroun d 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 enab les complete expression of the gene products encoded by the plasmids it del ivers into cultured cells. Finally, we have investigated the potential of M PG as an efficient delivery agent for gene therapy, by attempting to delive r antisense nucleic acids targeting an essential cell cycle gene. MPG effic iently delivered a plasmid expressing the full-length antisense cDNA of hum an cdc25C, which consequently successfully reduced cdc25C expression levels and promoted a block to cell cycle progression. Based on our results, we c onclude that MPG is a potent delivery agent for the generalised delivery of nucleic acids as well as of oligonucleotides into cultured cells and belie ve that its contribution to the development of new gene therapy strategies could be of prime interest.