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Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA

Nature Biotechnology volume 16, pages 355–358 (1998)Cite this article

Abstract

Peptide nucleic acid (PNA) is a DNA mimic with attractive properties for developing improved gene-targeted antisense agents. To test this potential of PNA in bacteria, PNAs were designed to target the start codon regions of the Escherichia coli β-galactosidase and β-lactamase genes. Dose-dependent and specific gene inhibition was observed in vitro using low nanomolar PNA concentrations and in vivo using low micromolar concentrations. Inhibition was more efficient for a permeable E. coli strain relative to wild-type K-12. The potency of the anti-β-lactamase PNAs was abolished by a six base substitution, and inhibition could be re-established using a PNA with compensating base changes. Antisense inhibition of the β-lactamase gene was sufficient to sensitize resistant cells to the antibiotic ampicillin. The results demonstrate gene- and sequence-specific antisense inhibition in E. coli and open possibilities for anti-sense antibacterial drugs and gene function analyses in bacteria.

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Author notes

  1. Peter E. Nielsen: e-mail:pen@biokemi.imbg.ku.dk

Authors and Affiliations

  1. Center for Biomolecular Recognition, IMBG, Department of Biochemistry B, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Copenhagen, Denmark

    Liam Good & Peter E. Nielsen

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  1. Liam Good
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  2. Peter E. Nielsen
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Good, L., Nielsen, P. Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA. Nat Biotechnol 16, 355–358 (1998). https://doi.org/10.1038/nbt0498-355

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