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

Nature Biotechnology
L Good, P E Nielsen

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 beta-galactosidase and beta-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-beta-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 beta-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 antisense antibacterial drugs and gene function analyses in bacteria.

References

Nov 27, 1992·Science·J C HanveyK G Au
Jan 1, 1988·Annual Review of Genetics·R W Simons, N Kleckner
May 20, 1989·Journal of Molecular Biology·M A SørensenS Pedersen
Dec 1, 1967·Proceedings of the National Academy of Sciences of the United States of America·M Sekiguchi, S Iida
Mar 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·K JayaramanP O Ts'o
May 22, 1995·FEBS Letters·P WittungB G Malmström
Sep 15, 1994·Biochemical Pharmacology·V V DemidovP E Nielsen
Apr 7, 1994·Nature·P WittungB Nordén
Feb 1, 1996·Nucleic Acids Research·H Knudsen, P E Nielsen
Feb 20, 1997·Nature·J W Nyce, W J Metzger
May 1, 1995·Journal of Peptide Science : an Official Publication of the European Peptide Society·L ChristensenR H Berg
Oct 15, 1998·Methods in Molecular Biology·J S ThorsonP G Schultz

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Citations

Sep 6, 2001·Biotechnology and Bioengineering·R SrivastavaW E Bentley
Nov 30, 2000·Current Infectious Disease Reports·D Knowles, G Patou
Jun 26, 2003·Trends in Pharmacological Sciences·Mario CazzolaClive P Page
May 12, 2000·Biochimica Et Biophysica Acta·H J LarsenP E Nielsen
Nov 10, 2000·Advanced Drug Delivery Reviews·D A Dean
Feb 5, 2003·Advanced Drug Delivery Reviews·Uffe Koppelhus, Peter E Nielsen
Feb 27, 1999·Current Opinion in Biotechnology·P E Nielsen
Mar 31, 1999·Bioorganic & Medicinal Chemistry Letters·W MaisonJ Martens
Mar 14, 2003·Drug Discovery Today·Bruce A Armitage
Jun 12, 2002·Current Opinion in Microbiology·Dezhong Yin, Yinduo Ji
May 5, 2001·Biomolecular Engineering·M PoogaU Langel
Nov 7, 2013·Molecular Therapy. Nucleic Acids·Nadja PatengeBernd Kreikemeyer
Apr 29, 1998·Nature Biotechnology·D J Ecker, S M Freier
Oct 29, 1999·European Journal of Biochemistry·H R DrewT Lockett
Dec 25, 2003·Journal of Biomolecular Structure & Dynamics·Olga V KrupnikYurii S Lazurkin
Jun 21, 2002·Antisense & Nucleic Acid Drug Development·Uffe KoppelhusPeter Eigil Nielsen
Nov 4, 2009·The Journal of Antimicrobial Chemotherapy·Brett L MellbyeBruce L Geller
Sep 19, 2012·Antimicrobial Agents and Chemotherapy·Susan E PuckettBruce L Geller
Sep 26, 2012·Antimicrobial Agents and Chemotherapy·Muhammad A Soofi, Mohamed N Seleem
Feb 22, 2001·Antimicrobial Agents and Chemotherapy·C Torres VieraR T Inouye
Sep 25, 2003·Antimicrobial Agents and Chemotherapy·B L GellerP L Iversen
Oct 25, 2003·Antimicrobial Agents and Chemotherapy·Guozhu ChenHerb E Schellhorn
Jan 9, 2010·Annual Review of Pharmacology and Toxicology·C Frank Bennett, Eric E Swayze
Dec 2, 2005·Journal of Molecular Microbiology and Biotechnology·Agné KulytéLiam Good
Aug 19, 2007·Microbial Cell Factories·Louise Carøe Vohlander RasmussenKim Kusk Mortensen
Dec 20, 2003·Pharmacogenomics·Dezhong YinYinduo Ji
Jan 3, 2012·International Journal of Medical Sciences·Rüdiger PipkornKlaus Braun
Feb 21, 2014·International Journal of Molecular Sciences·Nobutaka Nakashima, Kentaro Miyazaki
Mar 10, 2004·Expert Opinion on Biological Therapy·Violeta L MarinBruce A Armitage
Jul 5, 2005·Expert Opinion on Investigational Drugs·I Chopra
Jan 26, 2016·Journal of Medicinal Chemistry·Stefanie WagnerAlexander Titz

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