Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Inflammation
Published in: Inflammation 1/2017

01-02-2017 | REVIEW

Recent Advances in Aptamers Targeting Immune System

Author: Piao-Ping Hu

Published in: Inflammation | Issue 1/2017

Login to get access

Abstract

The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.
Appendix
Available only for authorised users
Literature
1.
Clark, R., and T. Kupper. 2005. Old meets new: the interaction between innate and adaptive immunity. The Journal of Investigative Dermatology 125: 629–637.CrossRefPubMed
2.
Engelke, C., A.V. Wiese, I. Schmudde, F. Ender, H.A. Strover, T. Vollbrandt, et al. 2014. Distinct roles of the anaphylatoxins C3a and C5a in dendritic cell-mediated allergic asthma. Journal of Immunology 193: 5387–5401.CrossRef
3.
Toben, C., and B.T. Baune. 2015. An Act of balance between adaptive and maladaptive immunity in depression: a role for T lymphocytes. Journal of Neuroimmune Pharmacology 10: 595–609.CrossRefPubMed
4.
Tuerk, C., and L. Gold. 1990. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249: 505–510.CrossRefPubMed
5.
Ellington, A.D., and J.W. Szostak. 1990. In vitro selection of RNA molecules that bind specific ligands. Nature 346: 818–22.CrossRefPubMed
6.
Groff K, Brown J, Clippinger AJ. 2015. Modern Affinity Reagents: Recombinant Antibodies and Aptamers. Biotechnol Adv.
7.
8.
Raddatz, M.S., A. Dolf, E. Endl, P. Knolle, M. Famulok, and G. Mayer. 2008. Enrichment of cell-targeting and population-specific aptamers by fluorescence-activated cell sorting. Angewandte Chemie (International Ed. in English) 47: 5190–5193.CrossRef
9.
Banerjee, J., and M. Nilsen-Hamilton. 2013. Aptamers: multifunctional molecules for biomedical research. Journal of Molecular Medicine (Berlin) 91: 1333–1342.CrossRef
10.
Gupta, S., M. Hirota, S.M. Waugh, I. Murakami, T. Suzuki, M. Muraguchi, et al. 2014. Chemically modified DNA aptamers bind interleukin-6 with high affinity and inhibit signaling by blocking its interaction with interleukin-6 receptor. The Journal of Biological Chemistry 289: 8706–8719.CrossRefPubMedPubMedCentral
11.
Liu, Y., T. Kwa, and A. Revzin. 2012. Simultaneous detection of cell-secreted TNF-alpha and IFN-gamma using micropatterned aptamer-modified electrodes. Biomaterials 33: 7347–7355.CrossRefPubMed
12.
Hwang, B., K. Han, and S.W. Lee. 2003. Prevention of passively transferred experimental autoimmune myasthenia gravis by an in vitro selected RNA aptamer. FEBS Letters 548: 85–89.CrossRefPubMed
13.
Pratico, E.D., B.A. Sullenger, and S.K. Nair. 2013. Identification and characterization of an agonistic aptamer against the T cell costimulatory receptor, OX40. Nucleic Acid Therapeutics 23: 35–43.CrossRefPubMedPubMedCentral
14.
Seth, R.B., L. Sun, and Z.J. Chen. 2006. Antiviral innate immunity pathways. Cell Research 16: 141–147.CrossRefPubMed
15.
Frazao, J.B., P.R. Errante, and A. Condino-Neto. 2013. Toll-like receptors’ pathway disturbances are associated with increased susceptibility to infections in humans. Archivum Immunologiae et Therapiae Experimentalis (Warsz) 61: 427–443.CrossRef
16.
17.
Chang, Y.C., W.C. Kao, W.Y. Wang, R.B. Yang, and K. Peck. 2009. Identification and characterization of oligonucleotides that inhibit Toll-like receptor 2-associated immune responses. The FASEB Journal 23: 3078–3088.CrossRefPubMed
18.
Hirsh, V., L. Paz-Ares, M. Boyer, R. Rosell, G. Middleton, W.E. Eberhardt, et al. 2011. Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer. Journal of Clinical Oncology 29: 2667–2674.CrossRefPubMed
19.
Krieg, A.M. 2012. CpG still rocks! Update on an accidental drug. Nucleic Acid Therapeutics 22: 77–89.PubMed
20.
Avci-Adali, M., H. Steinle, T. Michel, C. Schlensak, and H.P. Wendel. 2013. Potential capacity of aptamers to trigger immune activation in human blood. PloS One 8: e68810.CrossRefPubMedPubMedCentral
21.
Gilboa-Geffen, A., Y. Wolf, G. Hanin, N. Melamed-Book, M. Pick, E.R. Bennett, et al. 2011. Activation of the alternative NFkappaB pathway improves disease symptoms in a model of Sjogren’s syndrome. PloS One 6: e28727.CrossRefPubMedPubMedCentral
22.
Fukuda K, Tsujita T, Matsumoto M, Seya T, Sakiyama H, Nishikawa F, et al. 2006. Analysis of the interaction between human TLR3 ectodomain and nucleic acids. Nucleic Acids Symposium Series (Oxford): 249-250.
23.
24.
Iida, J., R. Clancy, J. Dorchak, R.I. Somiari, S. Somiari, M.L. Cutler, et al. 2014. DNA aptamers against exon v10 of CD44 inhibit breast cancer cell migration. PloS One 9: e88712.CrossRefPubMedPubMedCentral
25.
Cywinski, P.J., L. Olejko, and H.G. Lohmannsroben. 2015. A time-resolved luminescent competitive assay to detect L-selectin using aptamers as recognition elements. Analytica Chimica Acta 887: 209–215.CrossRefPubMed
26.
Kutlar, A., and S.H. Embury. 2014. Cellular adhesion and the endothelium: P-selectin. Hematology/Oncology Clinics of North America 28: 323–339.CrossRefPubMed
27.
Ernst, B., and J.L. Magnani. 2009. From carbohydrate leads to glycomimetic drugs. Nature Reviews. Drug Discovery 8: 661–677.CrossRefPubMed
28.
Burnette, A.D., S.M. Nimjee, M. Batchvarova, R. Zennadi, M.J. Telen, J. Nishimura, et al. 2011. RNA aptamer therapy for vaso-occlusion in sickle cell disease. Nucleic Acid Therapeutics 21: 275–283.CrossRefPubMed
29.
Ford, M.L., A.B. Adams, and T.C. Pearson. 2014. Targeting co-stimulatory pathways: transplantation and autoimmunity. Nature Reviews. Nephrology 10: 14–24.CrossRefPubMed
30.
Yeung, M.Y., N. Najafian, and M.H. Sayegh. 2014. Targeting CD28 to prevent transplant rejection. Expert Opinion on Therapeutic Targets 18: 225–242.CrossRefPubMed
31.
32.
Herrmann, A., S.J. Priceman, P. Swiderski, M. Kujawski, H. Xin, G.A. Cherryholmes, et al. 2014. CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells. The Journal of Clinical Investigation 124: 2977–2987.CrossRefPubMedPubMedCentral
33.
Pastor, F., M.M. Soldevilla, H. Villanueva, D. Kolonias, S. Inoges, A.L. de Cerio, et al. 2013. CD28 aptamers as powerful immune response modulators. Mol Ther Nucleic Acids 2: e98.CrossRefPubMedPubMedCentral
34.
Dollins, C.M., S. Nair, D. Boczkowski, J. Lee, J.M. Layzer, E. Gilboa, et al. 2008. Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer. Chemistry & Biology 15: 675–682.CrossRef
35.
Mallikaratchy, P.R., A. Ruggiero, J.R. Gardner, V. Kuryavyi, W.F. Maguire, M.L. Heaney, et al. 2011. A multivalent DNA aptamer specific for the B-cell receptor on human lymphoma and leukemia. Nucleic Acids Research 39: 2458–2469.CrossRefPubMed
36.
Mallikaratchy, P., Z. Tang, S. Kwame, L. Meng, D. Shangguan, and W. Tan. 2007. Aptamer directly evolved from live cells recognizes membrane bound immunoglobin heavy mu chain in Burkitt’s lymphoma cells. Molecular & Cellular Proteomics 6: 2230–2238.CrossRef
37.
Rus, H., C. Cudrici, and F. Niculescu. 2005. The role of the complement system in innate immunity. Immunologic Research 33: 103–112.CrossRefPubMed
38.
Wu, M., H. Li, Y. Zhang, and D. Chen. 2015. Development of a C3c-based ELISA method for the determination of anti-complementary potency of polysaccharides. Acta Pharmaceutica Sinica B 5: 316–322.CrossRefPubMedPubMedCentral
39.
Zipfel, P.F., J. Misselwitz, C. Licht, and C. Skerka. 2006. The role of defective complement control in hemolytic uremic syndrome. Seminars in Thrombosis and Hemostasis 32: 146–154.CrossRefPubMed
40.
Mooijaart, S.P., K.M. Koeijvoets, E.J. Sijbrands, M.R. Daha, and R.G. Westendorp. 2007. Complement Factor H polymorphism Y402H associates with inflammation, visual acuity, and cardiovascular mortality in the elderly population at large. Experimental Gerontology 42: 1116–1122.CrossRefPubMed
41.
Leung, E., and G. Landa. 2013. Update on current and future novel therapies for dry age-related macular degeneration. Expert Review of Clinical Pharmacology 6: 565–579.CrossRefPubMed
42.
Hoehlig, K., C. Maasch, N. Shushakova, K. Buchner, M. Huber-Lang, W.G. Purschke, et al. 2013. A novel C5a-neutralizing mirror-image (l-)aptamer prevents organ failure and improves survival in experimental sepsis. Molecular Therapy 21: 2236–2246.CrossRefPubMedPubMedCentral
43.
Stecker, J.R., A.A. Savage, J.G. Bruno, D.M. Garcia, and J.R. Koke. 2012. Dynamics and visualization of MCF7 adenocarcinoma cell death by aptamer-C1q-mediated membrane attack. Nucleic Acid Therapeutics 22: 275–282.PubMedPubMedCentral
44.
45.
Ma, J., M.G. Wang, A.H. Mao, J.Y. Zeng, Y.Q. Liu, X.Q. Wang, et al. 2013. Target replacement strategy for selection of DNA aptamers against the Fc region of mouse IgG. Genetics and Molecular Research 12: 1399–1410.CrossRefPubMed
46.
Nomura, Y., S. Sugiyama, T. Sakamoto, S. Miyakawa, H. Adachi, K. Takano, et al. 2010. Conformational plasticity of RNA for target recognition as revealed by the 2.15 A crystal structure of a human IgG-aptamer complex. Nucleic Acids Research 38: 7822–7829.CrossRefPubMedPubMedCentral
47.
Sugiyama, S., Y. Nomura, T. Sakamoto, T. Kitatani, A. Kobayashi, S. Miyakawa, et al. 2008. Crystallization and preliminary X-ray diffraction studies of an RNA aptamer in complex with the human IgG Fc fragment. Acta Crystallographica. Section F, Structural Biology and Crystallization Communications 64: 942–944.CrossRefPubMedPubMedCentral
48.
Miyakawa, S., Y. Nomura, T. Sakamoto, Y. Yamaguchi, K. Kato, S. Yamazaki, et al. 2008. Structural and molecular basis for hyperspecificity of RNA aptamer to human immunoglobulin G. RNA 14: 1154–1163.CrossRefPubMedPubMedCentral
49.
Yoshida, Y.S.N., H. Masuda, M. Furuichi, F. Nishikawa, S. Nishikawa, H. Mizuno, and I. Waga. 2008. Rabbit antibody detection with RNA aptamers. Analytical Biochemistry 375: 217–222.CrossRefPubMed
50.
Gokulrangan, G., J.R. Unruh, D.F. Holub, B. Ingram, C.K. Johnson, and G.S. Wilson. 2005. DNA aptamer-based bioanalysis of IgE by fluorescence anisotropy. Analytical Chemistry 77: 1963–1970.CrossRefPubMed
51.
Wiegand, T.W., P.B. Williams, S.C. Dreskin, M.H. Jouvin, J.P. Kinet, and D. Tasset. 1996. High-affinity oligonucleotide ligands to human IgE inhibit binding to Fc epsilon receptor I. Journal of Immunology 157: 221–230.
52.
Poongavanam, M.V., L. Kisley, K. Kourentzi, C.F. Landes, and R.C. Willson. 2016. Ensemble and single-molecule biophysical characterization of D17.4 DNA aptamer-IgE interactions. Biochimica et Biophysica Acta 1864: 154–164.CrossRefPubMed
53.
Boyle, J.J. 2005. Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. Current Vascular Pharmacology 3: 63–68.CrossRefPubMed
54.
Martin, P., and S.J. Leibovich. 2005. Inflammatory cells during wound repair: the good, the bad and the ugly. Trends in Cell Biology 15: 599–607.CrossRefPubMed
55.
Karin, N., and G. Wildbaum. 2015. The role of chemokines in shaping the balance between CD4(+) T cell subsets and its therapeutic implications in autoimmune and cancer diseases. Frontiers in Immunology 6: 609.CrossRefPubMedPubMedCentral
56.
Belladonna, M.L., and U. Grohmann. 2013. Bioengineering heterodimeric cytokines: turning promiscuous proteins into therapeutic agents. Biotechnology & Genetic Engineering Reviews 29: 149–174.CrossRef
57.
Francis, G.E., D. Fisher, C. Delgado, F. Malik, A. Gardiner, and D. Neale. 1998. PEGylation of cytokines and other therapeutic proteins and peptides: the importance of biological optimisation of coupling techniques. International Journal of Hematology 68: 1–18.CrossRefPubMed
58.
Brocker, C., D. Thompson, A. Matsumoto, D.W. Nebert, and V. Vasiliou. 2010. Evolutionary divergence and functions of the human interleukin (IL) gene family. Human Genomics 5: 30–55.CrossRefPubMedPubMedCentral
59.
Sung, H.J., S. Choi, J.W. Lee, C.Y. Ok, Y.S. Bae, Y.H. Kim, et al. 2014. Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8. Biomaterials 35: 578–589.CrossRefPubMed
60.
Berezhnoy, A., C.A. Stewart, J.O. McNamara 2nd, W. Thiel, P. Giangrande, G. Trinchieri, et al. 2012. Isolation and optimization of murine IL-10 receptor blocking oligonucleotide aptamers using high-throughput sequencing. Molecular Therapy 20: 1242–1250.CrossRefPubMedPubMedCentral
61.
Johnson, C., Y. Han, N. Hughart, J. McCarra, G. Alpini, and F. Meng. 2012. Interleukin-6 and its receptor, key players in hepatobiliary inflammation and cancer. Transl Gastrointest Cancer 1: 58–70.PubMedPubMedCentral
62.
Febbraio, M.A., S. Rose-John, and B.K. Pedersen. 2010. Is interleukin-6 receptor blockade the Holy Grail for inflammatory diseases? Clinical Pharmacology and Therapeutics 87: 396–398.CrossRefPubMed
63.
Li, S., N. Wang, and P. Brodt. 2012. Metastatic cells can escape the proapoptotic effects of TNF-alpha through increased autocrine IL-6/STAT3 signaling. Cancer Research 72: 865–875.CrossRefPubMed
64.
Zhang, H.Y., Q. Zhang, X. Zhang, C. Yu, X. Huo, E. Cheng, et al. 2011. Cancer-related inflammation and Barrett’s carcinogenesis: interleukin-6 and STAT3 mediate apoptotic resistance in transformed Barrett’s cells. American Journal of Physiology. Gastrointestinal and Liver Physiology 300: G454–460.CrossRefPubMed
65.
Hirota M, Murakami I, Ishikawa Y, Suzuki T, Sumida SI, Ibaragi S, et al. 2015. Chemically Modified Interleukin-6 Aptamer Inhibits Development of Collagen-Induced Arthritis in Cynomolgus Monkeys. Nucleic Acid Ther.
66.
Matharu, Z., D. Patel, Y. Gao, A. Haque, Q. Zhou, and A. Revzin. 2014. Detecting transforming growth factor-beta release from liver cells using an aptasensor integrated with microfluidics. Analytical Chemistry 86: 8865–8872.CrossRefPubMedPubMedCentral
67.
Kang, J., M.S. Lee, J.A. Copland 3rd, B.A. Luxon, and D.G. Gorenstein. 2008. Combinatorial selection of a single stranded DNA thioaptamer targeting TGF-beta1 protein. Bioorganic & Medicinal Chemistry Letters 18: 1835–1839.CrossRef
68.
Wordinger, R.J., T. Sharma, and A.F. Clark. 2014. The role of TGF-beta2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma. Journal of Ocular Pharmacology and Therapeutics 30: 154–162.CrossRefPubMedPubMedCentral
69.
Zhu, X., L. Li, L. Zou, G. Xian, H. Li, Y. Tan, et al. 2012. A novel aptamer targeting TGF-beta receptor II inhibits transdifferentiation of human tenon’s fibroblasts into myofibroblast. Investigative Ophthalmology & Visual Science 53: 6897–6903.CrossRef
70.
Zhu, X., D. Xu, L. Li, H. Li, F. Guo, X. Chen, et al. 2015. Evaluation of chitosan/aptamer targeting TGF-beta receptor II thermo-sensitive Gel for scarring in Rat glaucoma filtration surgery. Investigative Ophthalmology & Visual Science 56: 5465–5476.CrossRef
71.
Cao, B., Y. Hu, J. Duan, J. Ma, D. Xu, and X.D. Yang. 2014. Selection of a novel DNA aptamer for assay of intracellular interferon-gamma. PloS One 9: e98214.CrossRefPubMedPubMedCentral
72.
Ng, E.W., D.T. Shima, P. Calias, E.T. Cunningham Jr., D.R. Guyer, and A.P. Adamis. 2006. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nature Reviews. Drug Discovery 5: 123–132.CrossRefPubMed
73.
Zhou, J., Y. Shu, P. Guo, D.D. Smith, and J.J. Rossi. 2011. Dual functional RNA nanoparticles containing phi29 motor pRNA and anti-gp120 aptamer for cell-type specific delivery and HIV-1 inhibition. Methods 54: 284–294.CrossRefPubMedPubMedCentral
74.
Keefe, A.D., S. Pai, and A. Ellington. 2010. Aptamers as therapeutics. Nature Reviews. Drug Discovery 9: 537–550.CrossRefPubMed
75.
Sundaram, P., H. Kurniawan, M.E. Byrne, and J. Wower. 2013. Therapeutic RNA aptamers in clinical trials. European Journal of Pharmaceutical Sciences 48: 259–271.CrossRefPubMed
76.
Matsunaga, K., M. Kimoto, C. Hanson, M. Sanford, H.A. Young, and I. Hirao. 2015. Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications. Scientific Reports 5: 18478.CrossRefPubMedPubMedCentral
77.
Gilboa, E., J. McNamara 2nd, and F. Pastor. 2013. Use of oligonucleotide aptamer ligands to modulate the function of immune receptors. Clinical Cancer Research 19: 1054–1062.CrossRefPubMed
Metadata
Title
Recent Advances in Aptamers Targeting Immune System
Author
Piao-Ping Hu
Publication date
01-02-2017
Publisher
Springer US
Published in
Inflammation / Issue 1/2017
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-016-0437-9

Other articles of this Issue 1/2017

Inflammation 1/2017 Go to the issue

ORIGINAL ARTICLE

Angiotensin II-Induced Early and Late Inflammatory Responses Through NOXs and MAPK Pathways

ORIGINAL ARTICLE

Brain-Derived Neurotrophic Factor Inhibits Peptidoglycan-Induced Inflammatory Cytokine Expression in Human Dental Pulp Cells

ORIGINAL ARTICLE

Intranasal Curcumin Inhibits Pulmonary Fibrosis by Modulating Matrix Metalloproteinase-9 (MMP-9) in Ovalbumin-Induced Chronic Asthma

ORIGINAL ARTICLE

Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous Wound Healing

REVIEW

Aptamers Against Pro- and Anti-Inflammatory Cytokines: A Review

ORIGINAL ARTICLE

Genetic Phagocyte NADPH Oxidase Deficiency Enhances Nonviable Candida albicans–Induced Inflammation in Mouse Lungs
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits