Antisense and antigene properties of peptide nucleic acids.
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.
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D015247:Deoxyribonuclease HindIII / Q000037:antagonists & inhibitors; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000378:metabolism* / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000378:metabolism* / Q000494:pharmacology; D020135:Peptide Nucleic Acids; D010957:Plasmids; D014176:Protein Biosynthesis / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D000952:Antigens, Polyomavirus Transforming; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids; C078138:peptide nucleic acid, T10-lysine; D012313:RNA; D004247:DNA; D015247:Deoxyribonuclease HindIII