Related Experiment Video
Updated: Mar 24, 2026
In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
Considerations for the Characterization and Interpretation of Results Related to Alternative Complement Activation in
Scott P Henry1, Rosanne Seguin2, Joy Cavagnaro3
11 Preclinical Development, Ionis Pharmaceuticals, Inc. , Carlsbad, California.
Abstract:
This article provides an overview of the discussions held by the Immunomodulatory Subcommittee of the Oligonucleotide Safety Working Group on complement activation induced by oligonucleotides, most notably the phosphorothioate-containing oligonucleotides. Alternative complement pathway activation in monkeys is a common effect of single-stranded phosphorothioate backbone oligonucleotides in toxicology studies. This article discusses the mechanism for activation, general investigational strategy, and the impact of various chemical modifications. The goal is to provide the best practice approach to characterizing this effect, understanding the implication of the species specificity, and the interpretation of clinical relevance.
Insights
Phosphorothioate oligonucleotides can activate the alternative complement pathway, particularly in monkeys. This review details the mechanism, investigation strategies, and implications for clinical relevance.
Area of Science:
- Pharmacology
- Immunology
- Toxicology
Background:
- Phosphorothioate oligonucleotides are known to induce immune responses.
- Complement activation is a significant concern in oligonucleotide safety studies.
- The alternative complement pathway is frequently implicated.
Purpose of the Study:
- To summarize discussions on oligonucleotide-induced complement activation.
- To outline best practices for characterizing this effect.
- To clarify clinical relevance and species specificity.
Main Methods:
- Review of subcommittee discussions.
- Analysis of toxicology study data.
- Examination of chemical modification impacts.
Main Results:
- Alternative complement pathway activation is common in monkeys with single-stranded phosphorothioate oligonucleotides.
- Species specificity is a key consideration.
- Chemical modifications can influence activation.
Conclusions:
- Characterizing complement activation requires a strategic approach.
- Understanding species differences is crucial for interpreting results.
- Clinical relevance assessment is essential for oligonucleotide safety.
More Related Videos
09:54Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
11:55Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
Published on: March 14, 2011
Related Concept Videos
01:27Complement System
00:49Complementation Tests
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...