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.

JOURNAL ARTICLE Animal Antigens, Polyomavirus Transforming/GENETICS Cell Cycle/DRUG EFFECTS Cell Cycle Proteins/GENETICS Cell Line COS Cells Dose-Response Relationship, Drug DNA, Antisense/GENETICS/METABOLISM Fibroblasts/METABOLISM *Gene Transfer *Genetic Vectors Human HIV Envelope Protein gp41/GENETICS Luciferase/METABOLISM Mice Oligonucleotides/*GENETICS/METABOLISM Peptide Synthesis Peptides/*GENETICS Phosphoprotein Phosphatase/GENETICS Plasmids/METABOLISM Support, Non-U.S. Gov't 3T3 Cells

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