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• W2023452194 startingPage "1123" @default.
• W2023452194 abstract "Oligodeoxynucleotide phosphorothioates (PS-oligos) are being studied as novel therapeutic agents based on their ability to inhibit gene expression. Preclinical studies produced unanticipated complement and coagulation effects in monkeys receiving high-dose PS-oligo. In the present in vitro studies, PS-oligo inhibited normal human blood clotting as well as subsequent assays for prothrombin fragment PF1+2 and hemolytic complement. PS-oligo treatment of normal donor plasma produced concentration-dependent prolongations of clotting times, with the activated partial thromboplastin time more sensitive than prothrombin time or thrombin clotting time. PS-oligo treatment of normal donor serum similarly reduced hemolytic complement activity in a concentration-dependent manner. Reduced hemolysis correlated with increased levels of complement fragment C4d. The anti-heparin drug protamine sulfate inhibited in vitro effects of PS-oligo in both complement and coagulation assays, suggesting that charged residues in intemucleotide linkages of PS-oligo mediated the observed activities. Therefore, oligonucleotides with varying intemucleotide linkages, nucleotide sequence, or secondary structure were compared. Both complement and coagulation effects appeared to be independent of nucleotide sequence but were strongly related to the nature of intemucleotide linkages. Several of these modified oligonucleotides have been shown previously to retain potent antisense activity and thus may represent viable alternatives for antisense therapeutics." @default.
• W2023452194 created "2016-06-24" @default.
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• W2023452194 date "1997-04-01" @default.
• W2023452194 modified "2023-09-23" @default.
• W2023452194 title "Effects of synthetic oligonucleotides on human complement and coagulation∗" @default.
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• W2023452194 doi "https://doi.org/10.1016/s0006-2952(97)00091-9" @default.
• W2023452194 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9175717" @default.
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