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| Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA |
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| Author(s): Good L, Nielsen PE |
| Source: NATURE BIOTECHNOLOGY Volume: 16 Issue: 4 Pages: 355-358 Published: APR 1998 |
| Times Cited: 118 References: 26 |
| 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Nielsen, PE (reprint author), Univ Copenhagen, Panum Inst, Dept Biochem B, IMBG,Ctr Biomol Recognit, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark |
Addresses:
1. Univ Copenhagen, Panum Inst, Dept Biochem B, IMBG,Ctr Biomol Recognit, DK-2200 Copenhagen N, Denmark |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biotechnology & Applied Microbiology |
| IDS Number: ZE374 |
| ISSN: 1087-0156 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |