Bactericidal antisense effects of peptide-PNA conjugates

Citation
L. Good et al., Bactericidal antisense effects of peptide-PNA conjugates, NAT BIOTECH, 19(4), 2001, pp. 360-364
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biotecnology & Applied Microbiology",Microbiology
Journal title
NATURE BIOTECHNOLOGY
ISSN journal
1087-0156 → ACNP
Volume
19
Issue
4
Year of publication
2001
Pages
360 - 364
Database
ISI
SICI code
1087-0156(200104)19:4<360:BAEOPC>2.0.ZU;2-U
Abstract
Antisense peptide nucleic acids (PNAs) can specifically inhibit Escherichia coli gene expression and growth and hold promise as anti-infective agents and as tools for microbial functional genomics. Here we demonstrate that ch emical modification improves the potency of standard PNAs. We show that 9- to 12-mer PNAs, especially when attached to the cell wall/membrane-active p eptide KFFKFFKFFK, provide improvements in antisense potency in E. coli amo unting to two orders of magnitude while retaining target specificity. Pepti de-PNA conjugates targeted to ribosomal RNA (rRNA) and to messenger RNA (mR NA) encoding the essential fatty acid biosynthesis protein Acp prevented ce ll growth. The anti-acpP PNA at 2 muM concentration cured HeLa cell culture s noninvasively infected with E. coli K12 without any apparent toxicity to the human cells. These results indicate that peptides can be used to carry antisense PNA agents into bacteria. Such peptide-PNA conjugates open exciti ng possibilities for anti-infective drug development and provide new tools for microbial genetics.