The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.
Chemically Modified DNA Aptamers Bind Interleukin-6 with High Affinity and Inhibit Signaling by Blocking Its Interaction with Interleukin-6 Receptor
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Beyond cTnI, we expect that this scalable and reproducible top-down nanoproteomics approach can be generally applied to other low-abundance plasma/serum proteins of interest, such as cytokines or growth factors, if the NPs can be functionalized with a suitable affinity reagent55,56.”
From Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum (2020) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Tuerk, C., & Gold, L. (1990) · Science · doi:10.1126/science.2200121 · Cited by 10,421
In vitro selection of RNA molecules that bind specific ligands
Ellington, A. D., & Szostak, J. W. (1990) · Nature · doi:10.1038/346818a0 · Cited by 9,845
The pro- and anti-inflammatory properties of the cytokine interleukin-6
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.034 · Cited by 3,212
Pegaptanib for neovascular age-related macular degeneration
Gragoudas, E. S., Adamis, A. P., Cunningham, E. T., Feinsod, M., & Guyer, D. R. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa042760 · Cited by 2,337
Keefe, A. D., Pai, S., & Ellington, A. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3141 · Cited by 2,289
Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T., Kashiwamura, S.-I., Nakajima, K., Koyama, K., Iwamatsu, A., et al. (1986) · Nature · doi:10.1038/324073a0 · Cited by 2,139
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway
HEINRICH, P. C., BEHRMANN, I., MÜLLER-NEWEN, G., SCHAPER, F., & GRAEVE, L. (1998) · Biochemical Journal · doi:10.1042/bj3340297 · Cited by 2,130
Deoxynucleoside phosphoramidites—A new class of key intermediates for deoxypolynucleotide synthesis
Beaucage, S. L., & Caruthers, M. H. (1981) · Tetrahedron Letters · doi:10.1016/s0040-4039(01)90461-7 · Cited by 2,029
Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery
Gold, L., Ayers, D., Bertino, J., Bock, C., Bock, A., Brody, E. N., Carter, J., Dalby, A. B., Eaton, B. E., Fitzwater, T., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015004 · Cited by 1,754
Self-citationA Road Map for Those Who Don't Know JAK-STAT
Aaronson, D. S., & Horvath, C. M. (2002) · Science · doi:10.1126/science.1071545 · Cited by 1,371
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Zhao, 2013, Anti-IL-6 antibody Clazakizumab is more potent than Tocilizumab in blocking in vitroex vivo IL-6-induced functions, Arthritis and Rheumatism, 65
Cited by
Sorted by citations
Items 101–151 of 151
Biosensing Cytokine IL-6: A Comparative Analysis of Natural and Synthetic Receptors
Alfinito, E., Matteo Beccaria, A., & Ciccarese, M. (2020) · Biosensors · doi:10.3390/bios10090106 · Cited by 10
Ando, T., Yamamoto, M., Takamori, Y., Tsukamoto, K., Fuji, D., & Kawakami, T. (2021) · Bioscience Biotechnology and Biochemistry · doi:10.1093/bbb/zbaa124 · Cited by 10
Aptamer guided nanomedicine strategies in prostate cancer: Targeting and diagnosis
Shahrukh, S., Jain, N., Shah, S., Famta, P., Srinivasarao, D. A., Khatri, D. K., Asthana, A., Singh, S. B., Raghuvanshi, R. S., & Srivastava, S. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104593 · Cited by 10
Renders, M., Dumbre, S. G., Abramov, M., Kestemont, D., Margamuljana, L., Largy, E., Cozens, C., Vandenameele, J., Pinheiro, V. B., Toye, D., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz008 · Cited by 10
Borg, K. N., Ho, Y., & Zeng, S. (2024) · Advanced Optical Materials · doi:10.1002/adom.202400608 · Cited by 9
Multifunctional DNA nanomaterials: a new frontier in rheumatoid arthritis diagnosis and treatment
Zhang, Y., Sun, Y., Liao, H., & Shi, S. (2024) · Nanoscale · doi:10.1039/d4nr04013a · Cited by 9
Zhao, J. C., Katsube, S., Yamamoto, J., Yamasaki, K., Miyagishi, M., & Iwai, S. (2015) · The Analyst · doi:10.1039/c5an01347j · Cited by 9
The use of aptamers as therapeutic inhibitors and biosensors of TNF-alpha
Samiei-Abianeh, H., Kesharwani, P., & Sahebkar, A. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.141202 · Cited by 9
Harmonic phase angles used for nanoparticle sensing
Shi, Y., Khurshid, H., Ness, D. B., & Weaver, J. B. (2017) · Physics in Medicine and Biology · doi:10.1088/1361-6560/aa8a4a · Cited by 9
Antibody‐ and aptamer‐strategies for Gv HD prevention
Oelkrug, C., Sack, U., Boldt, A., Nascimento, I. C., Ulrich, H., & Fricke, S. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12416 · Cited by 9
In silico analysis of aptamer-RNA conjugate interactions with human transferrin receptor
Vasconcelos, D., Pina, A. F., Habib, N., & Sousa, S. F. (2024) · Biophysical Chemistry · doi:10.1016/j.bpc.2024.107308 · Cited by 8
Exploring the diagnostic landscape: Portable aptasensors in point-of-care testing
Mohan, A., & Roy, I. (2025) · Analytical Biochemistry · doi:10.1016/j.ab.2025.115788 · Cited by 9
Nanoparticles Fueled by Enzyme for the Treatment of Hyperlipidemic Acute Pancreatitis
Chen, G., Huang, Y.-F., Yu, H., Wang, J., Li, H., Shen, S., Zhou, X., Shi, K., & Sun, H. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.4c00474 · Cited by 8
Clinical use and future perspective of aptamers
Esawi, E., Nsairat, H., Mahmoud, I. S., Lafi, Z. M., Al-Kadash, A., Alragheb, B. A., Ismail, S. I., & Alhaer, W. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-85881-6.00013-0 · Cited by 8
DNA display of folded RNA libraries enabling RNA-SELEX without reverse transcription
MacPherson, I. S., Temme, J. S., & Krauss, I. J. (2017) · Chemical Communications · doi:10.1039/c6cc09991b · Cited by 8
Nucleic Acids for Potential Treatment of Rheumatoid Arthritis
Sun, P., Su, J., Wang, X., Zhou, M., Zhao, Y., & Gu, H. (2022) · ACS Applied Bio Materials · doi:10.1021/acsabm.1c01205 · Cited by 8
Aptamers Targeting Immune Checkpoints for Tumor Immunotherapy
Abdu, A. M. A., Liu, Y., Abduljabbar, R., Man, Y., Chen, Q., & Liu, Z. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17080948 · Cited by 7
Exploiting the Nucleic Acid Nature of Aptamers for Signal Amplification
Jauset‐Rubio, M., Ortiz, M., & O’Sullivan, C. K. (2022) · Biosensors · doi:10.3390/bios12110972 · Cited by 7
Yang, J., Tabuchi, Y., Katsuki, R., & Taki, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043525 · Cited by 8
Selection and characterization of single-stranded DNA aptamers against interleukin-5
Khanahmad, H., Jamalvandi, M., Irani, S., & Bastaminezhad, S. (2019) · Research in Pharmaceutical Sciences · doi:10.4103/1735-5362.272560 · Cited by 7
Nanoparticles Advancing Cancer Immunotherapy
Chowdhury, M. M. H., Kubra, K., Kanwar, R. K., & Kanwar, J. R. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815889-0.00013-1 · Cited by 6
In vitro selection technologies to enhance biomaterial functionality
Rosch, J. C., Hollmann, E. K., & Lippmann, E. S. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216647182 · Cited by 6
Development of an Aptamer-Based Electrochemical Microfluidic Device for Viral Vaccine Quantitation
Chozinski, T. J., Ferguson, B. S., Fisher, W. S., Ge, S., Gong, Q., Kang, H., McDermott, J., Scott, A., Shi, W., Trausch, J. J., et al. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.1c05093 · Cited by 6
Percze, K., Tolnai, Z. J., Eleveld, M. J., Ou, L., Du, H., Olia, A. S., Kwong, P. D., de Jonge, M. I., & Mészáros, T. (2023) · Scientific Reports · doi:10.1038/s41598-023-36428-2 · Cited by 5
Nucleic Acid‐Templated Synthesis of Sequence‐Defined Synthetic Polymers
Chen, Z., & Liu, D. R. (2017) · Wiley eBooks · doi:10.1002/9783527806096.ch3 · Cited by 5
Aptamer-functionalized biomaterials for bone-related diseases therapy
Li, Q., & Zhang, M. (2025) · Cell Biomaterials · doi:10.1016/j.celbio.2025.100272 · Cited by 4
Kim, N., Le, H. T., Yang, Y., Byun, K. M., & Kim, T. W. (2015) · Bulletin of the Korean Chemical Society · doi:10.1002/bkcs.10524 · Cited by 4
Engineering DNA Switches for DNA Computing Applications
Lauzon, D., Zhu, G., & Vallée‐Bélisle, A. (2021) · doi:10.1002/9783527825424.ch7 · Cited by 4
Lobo-Castañón, M. J., & Díaz‐Fernández, A. (2025) · Biosensors · doi:10.3390/bios15110726 · Cited by 3
The emerging role of aptamers in targeted cancer immunotherapy
Zhu, S., Xu, R., Xu, H., Wang, Y., Wang, L., He, N. S. M., Wang, H.-H., & Ren, X. (2025) · Molecular Therapy Oncology · doi:10.1016/j.omton.2025.201110 · Cited by 3
Aptamer-based PSA biosensing technology: From nanomaterials to CRISPR-diagnostics technology
Guo, X., Zhang, J., Han, K., Li, Y., & Wang, D. (2025) · Talanta · doi:10.1016/j.talanta.2025.128871 · Cited by 3
Aptamers and Clinical Applications
Zon, G. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788015714-00367 · Cited by 3
Energy Transfer as A Driving Force in Nucleic Acid–Protein Interactions
Zavyalova, E. G., & Kopylov, A. M. (2019) · Molecules · doi:10.3390/molecules24071443 · Cited by 3
APTAMER PROPERTIES, FUNCTIONS, AND APPLICATIONS
Tan, W., Zhao, Z., & Zhang, L. (2022) · doi:10.1002/9781119692799.ch13 · Cited by 3
A new method for the reproducible development of aptamers (Neomers)
Meehan, C., Hamilton, E. L., Mansour, C. G., Lecocq, S., Drake, C. J., An, Y., Rodrigues, E., & Penner, G. (2025) · PLoS ONE · doi:10.1371/journal.pone.0311497 · Cited by 4
Aptamers as a Promising Therapeutic Tool for Cancer Immunotherapy
Soldevilla, M. M., Villanueva, H., & Pastor, F. (2017) · InTech eBooks · doi:10.5772/66964 · Cited by 2
Magnetically Detected Protein Binding Using Spin-Labeled Slow Off-Rate Modified Aptamers
Lu, S., Fowler, C. R., Ream, B. E., Waugh, S. M., Russell, T. M., Rohloff, J. C., Gold, L., Cleveland, J. P., & Stoll, S. (2023) · ACS Sensors · doi:10.1021/acssensors.3c00112 · Cited by 2
Self-citationRecent advancements in aptamer-mediated theranostics in the management of hematological disorders
Ganguly, S. C., Paul, R., Mondal, B., Kundu, M., & Chakraborty, T. (2025) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2025.126435 · Cited by 1
Design and Biological Application of RTK Agonist Aptamers
Ueki, R., & Sando, S. (2022) · Springer eBooks · doi:10.1007/978-981-16-1313-5_78-1 · Cited by 1
Aptamers in the Treatment of Bacterial Infections: Problems and Prospects
Zeninskaya, N. A., Kolesnikov, A. V., Ryabko, A. K., Shemyakin, I. G., Dyatlov, I. A., & Владимировна, К. А. (2016) · Annals of the Russian academy of medical sciences · doi:10.15690/vramn591 · Cited by 1
Design and Biological Application of RTK Agonist Aptamers
Ueki, R., & Sando, S. (2023) · Springer eBooks · doi:10.1007/978-981-19-9776-1_78 · Cited by 1
InChemicoModification of Nucleotides for Better Recognition
Jurek, P., Matusiewicz, M., Mazurek, M., & Jeleń, F. (2018) · Wiley eBooks · doi:10.1002/9783527806799.ch2 · Cited by 1
An investigation into the structure and specificity of a G-Quadruplex RNA-aptamer
Szameit, K. (2016) · Max Planck Digital Library
Prodeus, A. (2018) · TSpace (University of Toronto)
Additional file 1 of Targeting IL-6 by engineered Lactococcus lactis via surface-displayed affibody
Zahirović, A., & Berlec, A. (2022) · Figshare · doi:10.6084/m9.figshare.20329618
Dobrokhotov, I. V., Yakushenko, E. V., Kudryashova, N. O., & Moskalev, A. A. (2025) · Fizioterapevt (Physiotherapist) · doi:10.33920/med-14-2505-10
Bouvier‐Müller, A. (2020) · theses.fr (ABES) · doi:10.70675/2097d129z95aaz45f5zbf91z199fddefb42c
RNA therapeutics: current status and future directions
Yang, B., Sedano, M. J., Perez, K. L., Vijayaraghavan, M., Reid, V. A., Yallapu, M. M., Chauhan, S. C., Dhandayuthapani, S., Ramos, E., & Gadad, S. S. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-03032-5 · Cited by 1
Stabilizing Functional Nucleic Acids for Real‐Sample Diagnostics
Lee, S., Dondi, L., Mathai, A., Nurmi, C., & Li, Y. (2026) · Angewandte Chemie · doi:10.1002/ange.1386648
Stabilizing Functional Nucleic Acids for Real‐Sample Diagnostics
Lee, S., Dondi, L., Mathai, A., Nurmi, C., & Li, Y. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.1386648
Metadata
- Authors
- Gupta, S., Hirota, M., Waugh, S. M., Murakami, I., Suzuki, T., Muraguchi, M., Shibamori, M., Ishikawa, Y., Jarvis, T. C., Carter, J. D., Zhang, C., Gawande, B., Vrkljan, M., Janjic, N., & Schneider, D. J.
- Affiliations
- SomaLogic (United States) (US)
- Corresponding author
- Schneider, Daniel J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 289
- Issue
- 12
- Pages
- 8706-8719
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3961692
- OpenAlex
- W2084203294
- Cited by
- 151
- References
- 52
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 7 · 2023: 10 · 2022: 16 · 2021: 9 · 2020: 13 · 2019: 17 · 2018: 14 · 2017: 13 · 2016: 14 · 2015: 16 · 2014: 6
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- interleukin-6, SOMAmer, IL-6 receptor, cytokine signaling inhibition, SELEX, serum stability, tumor cell proliferation, inflammatory diseases
- MeSH terms
- Interleukin-6 Inhibitors, Amino Acid Sequence, Animals, Anti-Inflammatory Agents, Base Sequence, Cricetulus, Humans, Macaca fascicularis, Molecular Sequence Data, Interleukin-6, CHO Cells, Receptors, Interleukin-6, Serum, Mice, Rats, SELEX Aptamer Technique, Aptamers, Nucleotide, Drug Discovery
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
