ArticleJournal of immunology (Baltimore, Md. : 1950)2015
A New Approach for the Treatment of Arthritis in Mice with a Novel Conjugate of an Anti-C5aR1 Antibody and C5 Small Interfering RNA.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Antibody-oligonucleotide conjugates: an emerging modality for precision RNA therapeutics.Antibody therapeutics · 2026Review
- Large-scale molecular endotype discovery in synovial fluid reveals osteoarthritis as a single biological continuum.Nature communications · 2026Article
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- An Overview of the Development and Preclinical Evaluation of Antibody-Drug Conjugates for Non-Oncological Applications.Pharmaceutics · 2023Review
- Potential causal role of synovial complement system activation in the development of post-traumatic osteoarthritis after anterior cruciate ligament injury or meniscus tear.Frontiers in immunology · 2023Article
- Analysis of Complement Gene Expression, Clinical Associations, and Biodistribution of Complement Proteins in the Synovium of Early Rheumatoid Arthritis Patients Reveals Unique Pathophysiologic Features.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Evolution of complexity in non-viral oligonucleotide delivery systems: from gymnotic delivery through bioconjugates to biomimetic nanoparticles.RNA biology · 2022Review
- Antibody-Drug Conjugates: Functional Principles and Applications in Oncology and Beyond.Vaccines · 2021Review
- Targeting Complement C5a Receptor 1 for the Treatment of Immunosuppression in Sepsis.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Antibody Conjugates-Recent Advances and Future Innovations.Antibodies (Basel, Switzerland) · 2020Review
- Key Components of the Complement Lectin Pathway Are Not Only Required for the Development of Inflammatory Arthritis but Also Regulate the Transcription of Factor D.Frontiers in immunology · 2020Article
- C2 IgM Natural Antibody Enhances Inflammation and Its Use in the Recombinant Single Chain Antibody-Fused Complement Inhibitor C2-Crry to Target Therapeutics to Joints Attenuates Arthritis in Mice.Frontiers in immunology · 2020Article
- Applications of RNA interference in the treatment of arthritis.Translational research : the journal of laboratory and clinical medicine · 2019Review
- Evaluation of Targeting Efficiency of Joints with Anticollagen II Antibodies.Molecular pharmaceutics · 2019Article
- Significance of Complement System in Ischemic Stroke: A Comprehensive Review.Aging and disease · 2019Review
- Targeting of Liver Mannan-Binding Lectin-Associated Serine Protease-3 with RNA Interference Ameliorates Disease in a Mouse Model of Rheumatoid Arthritis.ImmunoHorizons · 2018Article
- Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Rheumatoid arthritis (RA) is an inflammatory autoimmune joint disease in which the complement system plays an important role. Of the several components of complement, current evidence points to C5 as the most important inducer of inflammation. Several groups generated Abs or small interfering RNAs (siRNAs) or small molecule inhibitors against C5 and C5aR1 (CD88) that have showed some efficacy in RA in animal models. However, none of these candidate therapeutics has moved from bench to bedside. In this study, we test in collagen Ab-induced arthritis (CAIA) a new therapeutic strategy using a novel anti-C5ab-C5 siRNA conjugate. We first demonstrate that although C5aR2 or C5L2 (GPR77) plays no role in CAIA, C5aR1 contributes to pathogenesis. We demonstrate that injection of siRNAs blocking C5, C5aR1, or the combination decreased clinical disease activity in mice with CAIA by 45%, 51%, and 58%, respectively. Anti-C5 Ab (BB5.1) has only limited efficacy, but significantly reduced arthritis up to 66%. We then generated a novel anti-C5aR1 Ab-protamine-C5 siRNA conjugate. To our knowledge, we show for the first time that whereas unconjugated Ab plus siRNAs reduce arthritis by 19%, our anti-C5aR1 Ab-protamine-C5 siRNA conjugate was effective in reducing arthritis by 83% along with a parallel decrease in histopathology, C3 deposition, neutrophils, and macrophages in the joints of mice with CAIA. These data suggest that by targeting anti-C5 siRNAs to the receptor for its C5a activation fragment (C5aR1), a striking clinical effect can be realized.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.