Stereodependent Inhibition of Plasminogen Activator Inhibitor Type 1 by Phosphorothioate Oligonucleotides: Proof of Sequence Specificity in Cell Culture andIn VivoRat Experiments
- 1 December 1997
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antisense and Nucleic Acid Drug Development
- Vol. 7 (6) , 567-573
- https://doi.org/10.1089/oli.1.1997.7.567
Abstract
Hexadecadeoxyribonucleotides complementary to a fragment of human PAI-1 mRNA located upstream of the start codon and their phosphorothioate analogs were studied in cultured HUVECs as sequence-dependent inhibitors of PAI-1 expression. The activity of the random mixture of diastereomers of phosphorothioate hexadecanucleotide PS-16H has been compared with that of isosequential, stereoregular [All-SP] and [All-RP] isomers. The highest inhibitory effect on PAI-1 synthesis was observed with the [A11-SP] diastereomer. Stereorandom phosphorothioate oligonucleotide PS-16R complementary to the same region of rat PAI-1 mRNA, when injected into tail vein of rats, substantially decreased the level of PAI-1 in blood plasma.Keywords
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