ArticleThe Journal of biological chemistry2014
Chemically modified DNA aptamers bind interleukin-6 with high affinity and inhibit signaling by blocking its interaction with interleukin-6 receptor.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 150 citations in OpenAlex.
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Expedient single-round selection of hyper-modified aptamer targeting insulin receptor from over-represented dually nucleobase-modified DNA libraries.Nature communications · 2026Article
- The emerging role of aptamers in targeted cancer immunotherapy.Molecular therapy. Oncology · 2026Review
- Aptamers targeting immune checkpoints for tumor immunotherapy: a comprehensive review.Frontiers in oncology · 2026Review
- Aptamer-Based Strategies for Colorectal Cancer Detection: Emerging Technologies and Future Directions.Biosensors · 2025Review
- Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders.Bone research · 2025Review
- Aptamers Targeting Immune Checkpoints for Tumor Immunotherapy.Pharmaceutics · 2025Review
- Hybrid Aptamer Molecularly Imprinted Polymer Nanoparticles for Reducing Oxidized Low-Density Lipoprotein Internalization by Macrophages.ACS applied materials & interfaces · 2025Article
- Nanoparticles Fueled by Enzyme for the Treatment of Hyperlipidemic Acute Pancreatitis.ACS biomaterials science & engineering · 2024Article
- Evolution of a bispecific G-quadruplex-forming circular aptamer to block IL-6/sIL-6R interaction for inflammation inhibition.Chemical science · 2024Article
- Selection of optimised ligands by fluorescence-activated bead sorting.Chemical science · 2023Article
- Tryptophan-like side chain holding aptamers inhibit respiratory syncytial virus infection of lung epithelial cells.Scientific reports · 2023Article
- Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic acids research · 2023Review
- Broadly neutralizing aptamers to SARS-CoV-2: A diverse panel of modified DNA antiviral agents.Molecular therapy. Nucleic acids · 2023Article
- bioTCIs: Middle-to-Macro Biomolecular Targeted Covalent Inhibitors Possessing Both Semi-Permanent Drug Action and Stringent Target Specificity as Potential Antibody Replacements.International journal of molecular sciences · 2023Review
- A Review on Bio- and Chemosensors for the Detection of Biogenic Amines in Food Safety Applications: The Status in 2022.Sensors (Basel, Switzerland) · 2023Review
- Advances in Aptamers-Based Applications in Breast Cancer: Drug Delivery, Therapeutics, and Diagnostics.International journal of molecular sciences · 2022Review
- Article
- Inhibition of Autophagy Promotes the Elimination of Liver Cancer Stem Cells by CD133 Aptamer-Targeted Delivery of Doxorubicin.Biomolecules · 2022Article
- Targeting IL-6 by engineered Lactococcus lactis via surface-displayed affibody.Microbial cell factories · 2022Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates immune and inflammatory responses, and its overproduction is a hallmark of inflammatory diseases. Inhibition of IL-6 signaling with the anti-IL-6 receptor antibody tocilizumab has provided some clinical benefit to patients; however, direct cytokine inhibition may be a more effective option. We used the systematic evolution of ligands by exponential enrichment (SELEX) process to discover slow off-rate modified aptamers (SOMAmers) with hydrophobic base modifications that inhibit IL-6 signaling in vitro. Two classes of IL-6 SOMAmers were isolated from modified DNA libraries containing 40 random positions and either 5-(N-benzylcarboxamide)-2'-deoxyuridine (Bn-dU) or 5-[N-(1-naphthylmethyl)carboxamide]-2'-deoxyuridine (Nap-dU) replacing dT. These modifications facilitate the high affinity binding interaction with IL-6 and provide resistance against degradation by serum endonucleases. Post-SELEX optimization of one Bn-dU and one Nap-dU SOMAmer led to improvements in IL-6 binding (10-fold) and inhibition activity (greater than 20-fold), resulting in lead SOMAmers with sub-nanomolar affinity (Kd = 0.2 nm) and potency (IC50 = 0.2 nm). Although similar in inhibition properties, the two SOMAmers have unique sequences and different ortholog specificities. Furthermore, these SOMAmers were stable in human serum in vitro for more than 48 h. Both SOMAmers prevented IL-6 signaling by blocking the interaction of IL-6 with its receptor and inhibited the proliferation of tumor cells in vitro as effectively as tocilizumab. This new class of IL-6 inhibitor may be an effective therapeutic alternative for patients suffering from inflammatory diseases.
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