Peptide nucleic acids as antibacterial agents via the antisense principle

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Abstract
Peptide nucleic acid (PNA) is a peptide-like DNA mimic that was introduced almost ten years ago. It was immediately predicted that PNA would have a bright future in gene therapeutic drug development, but progress in this direction has been rather modest thus far. This is predominantly due to inefficient uptake of PNA by most living cells. However, within the past couple of years a variety of methods have been devised to address this problem and the stage should now be set for more rapid progress. Several studies have demonstrated antisense effects ex vivo in cells in culture and two reports on direct injection of PNA into the brain of rats are also interesting. Only a few studies have addressed the possible exploitation of the antisense principle for development of antibacterial drugs. However, the first in vitro results using antiribosomal RNA PNAs and antisense PNAs targeted to the beta-lactamase gene on Escherichia coli cultures were quite promising. Most recently, these preliminary studies have been extended to demonstrate in vivo efficacy of antibacterial PNAs in an E. coli peritonitis/sepsis mouse model. Therefore, PNA drug development again is rapidly picking up pace.