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Science 27 November 1992:
Vol. 258. no. 5087, pp. 1481 - 1485
DOI: 10.1126/science.1279811
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Articles
Science, Vol 258, Issue 5087, 1481-1485
Copyright © 1992 by American Association for the Advancement of Science
Antisense and antigene properties of peptide nucleic acids
JC Hanvey,
NJ Peffer,
JE Bisi,
SA Thomson,
R Cadilla,
JA Josey,
DJ Ricca,
CF Hassman,
MA Bonham,
KG Au,
and
al. et
Department of Cell Biology, Glaxo Inc. Research Institute, Research Triangle Park, NC 27709.
Peptide nucleic acids (PNAs) are polyamide oligomers that can strand invade duplex DNA, causing displacement of one DNA strand and formation of a D-loop. Binding of either a T10 PNA or a mixed sequence 15-mer PNA to the transcribed strand of a G-free transcription cassette caused 90 to 100 percent site-specific termination of pol II transcription elongation. When a T10 PNA was bound on the nontranscribed strand, site-specific inhibition never exceeded 50 percent. Binding of PNAs to RNA resulted in site-specific termination of both reverse transcription and in vitro translation, precisely at the position of the PNA.RNA heteroduplex. Nuclear microinjection of cells constitutively expressing SV40 large T antigen (T Ag) with either a 15-mer or 20-mer PNA targeted to the T Ag messenger RNA suppressed T Ag expression. This effect was specific in that there was no reduction in beta-galactosidase expression from a coinjected expression vector and no inhibition of T Ag expression after microinjection of a 10-mer PNA.
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