Antisense effect of oligodeoxynucleotides with inverted terminal internucleotidic linkages: a minimal modification protecting against nucleolytic degradation.
The synthesis of a new class of antisense oligonucleotide compounds with 3'-3' and 5'-5' end inversion (INV-oligonucleotides) is described. Besides the advantage of simplicity of synthesis, physico-chemical studies show that these compounds do not disturb Watson-Crick base-pairing. INV-oligonucleotides have a half-life of 30 h in human serum. We show that they are capable of inhibiting SV40 large T-antigen expression in COS-1 cells, both in vitro and in vivo, and by modulation of the expression of cellular oncoprotein p53 in vitro.
Ortigão
J F
JF
Sektion Polymere, Universität Ulm, Germany.
Rösch
H
H
Selter
H
H
Fröhlich
A
A
Lorenz
A
A
Montenarh
M
M
Seliger
H
H
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011233:Precipitin Tests; D014176:Protein Biosynthesis / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D016376:Oligonucleotides, Antisense; D016159:Tumor Suppressor Protein p53