Novel enzymatic and immunological responses to oligonucleotides

Toxicology Letters
S AgrawalD R Shaw

Abstract

Oligonucleotide phosphorothioates (PS-oligos) are being studied as antisense agents for viral infection and cancer. In preclinical studies, PS-oligos produced dose-dependent changes in heart rate and blood pressure and significantly reduced serum hemolytic complement, which could be avoided by slowing infusion rates. Here, in vitro PS-oligo treatment of either human, rhesus monkey or guinea pig serum reduced hemolytic complement and further inhibited in vitro coagulation when added to whole blood or citrated plasma. These effects were dependent upon both oligonucleotide dose and structure. Oligonucleotides having identical sequences but containing methylphosphonates (Chimeric), 2'-O-methyl ribonucleosides (Hybrid) or 3' hairpin loop (Self-stabilized) had altered effects on complement and coagulation in vitro.

References

Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S AgrawalT Pederson
Jan 1, 1995·Clinical Pharmacokinetics·S AgrawalJ Tang
Feb 1, 1995·Current Opinion in Biotechnology·S Agrawal, R P Iyer
Jul 1, 1961·Proceedings of the Society for Experimental Biology and Medicine·D F HERSEY, F D MAURER
Dec 1, 1961·Annals of Internal Medicine·S S KALTER

❮ Previous
Next ❯

Citations

Apr 16, 1998·Pharmacology & Therapeutics·S Agrawal, R P Iyer
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·K P WilliamsD P Bartel
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·S AgrawalR Zhang
Jun 16, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fuxin Shi, Dick Hoekstra
Dec 25, 2019·Nucleic Acid Therapeutics·Melina ChristouNikolaos P Mastroyiannopoulos
Mar 10, 2004·Biological Reviews of the Cambridge Philosophical Society·William G Eberhard
Oct 1, 1996·Trends in Biotechnology·S Agrawal

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.