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Science ; 258(5087): 1481-5, 1992 Nov 27.
Article in English | MEDLINE | ID: mdl-1279811

ABSTRACT

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.


Subject(s)
DNA/metabolism , Oligodeoxyribonucleotides/metabolism , Oligonucleotides, Antisense/metabolism , Peptide Nucleic Acids , Animals , Antigens, Polyomavirus Transforming/genetics , Base Sequence , Deoxyribonuclease HindIII/antagonists & inhibitors , Gene Expression/drug effects , HeLa Cells , Humans , In Vitro Techniques , Molecular Sequence Data , Oligodeoxyribonucleotides/pharmacology , Oligonucleotides, Antisense/pharmacology , Plasmids , Protein Biosynthesis/drug effects , RNA/metabolism , Rabbits , Rats , Transcription, Genetic/drug effects
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