Complement Activation and Hemodynamic Changes Following Intravenous Administration of Phosphorothioate Oligonucleotides in the Monkey
- 1 January 1994
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antisense Research and Development
- Vol. 4 (3) , 201-206
- https://doi.org/10.1089/ard.1994.4.201
Abstract
Rapid intravenous infusion of GEM 91, a 25-mer phosphorothioate oligonucleotide complementary to the gag site of HIV, in the monkey produces transient decreases in peripheral total WBC and neutrophil counts, hemoconcentration, and a brief increase followed by a prolonged decrease in arterial blood pressure. These changes are preceded by and are likely mediated by activation of C5 complement. These effects are dose and infusion rate dependent and can be avoided by administering GEM 91 by slow intravenous infusion. Similar hemodynamic effects are produced with rapid intravenous infusion of other phosphorothioate oligonucleotides varying in length from 20- to 33-mer, and are, therefore, not sequence specific but a property of this chemical structure.Keywords
This publication has 12 references indexed in Scilit:
- Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells.Proceedings of the National Academy of Sciences, 1994
- Large-Scale Synthesis, Purification, and Analysis of Oligodeoxynucleotide PhosphorothioatesAntisense Research and Development, 1994
- Antiviral activity of a phosphorothioate oligonucleotide complementary to RNA of the human cytomegalovirus major immediate-early regionAntimicrobial Agents and Chemotherapy, 1993
- Long-term treatment of human immunodeficiency virus-infected cells with antisense oligonucleotide phosphorothioates.Proceedings of the National Academy of Sciences, 1993
- In vitro evaluation of phosphorothioate oligonucleotides targeted to the E2 mRNA of papillomavirus: potential treatment for genital wartsAntimicrobial Agents and Chemotherapy, 1993
- Systemic Administration of a Phosphorothioate Oligonucleotide with a Sequence Complementary to p53 for Acute Myelogenous Leukemia and Myelodysplastic Syndrome: Initial Results of a Phase I TrialAntisense Research and Development, 1993
- Antisense oligonucleotides as antiviral agentsTrends in Biotechnology, 1992
- Antimalarial activities of oligodeoxynucleotide phosphorothioates in chloroquine-resistant Plasmodium falciparum.Proceedings of the National Academy of Sciences, 1992
- GEM* 91—An Antisense Oligonucleotide Phosphorothioate as a Therapeutic Agent for AIDSAntisense Research and Development, 1992
- Increased Expression of an Adhesion-Promoting Surface Glycoprotein in the Granulocytopenia of HemodialysisNew England Journal of Medicine, 1985