Organ-on-a-Chip: The Future of Therapeutic Aptamer Research?


The aptamer, known as a chemical antibody, has proven to be of high diagnostic and therapeutic value with the FDA’s first aptamer drug in 2004 and many aptamers under clinical validation. However, the clinical translation of aptamer for therapeutics has been delayed because of the limitation of using the target model during selection and a lack of information on several crucial factors, including their inherent physicochemical characterization and safety, and the function. Three-dimensional (3D) structure tissue provides proof of in-depth functionality due to their maturity and 3D complexity, enabling them to get information on the natural structure of the target for human treatment. The organ-on-a-chip integrates microfluidic technology with 3D cell culture that possesses in vivo-like tissue-based models that have been engineered for validation to transform the commercial drug discovery. Thus, the organ-on-a-chip may offer a promising solution for the addressed problems, enhancing the clinical translation procedure for aptamer-based therapeutics. Motivated by the advantageous function of the aptamer-based organ-on-a-chip system, we update the current technology to generate aptamers using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) and confirm the application of aptamers to various long-term treatments. We can also accurately analyze the advantages of organ-on-a-chips and present the necessity of developing aptamer-based organ-on-a-chip systems. In this regard, the aptamer-based organ-on-a-chip is expected to increase the possibility of creating an aptamer as a therapeutic agent by more accurately selecting and verifying the aptamer that affects specific organ treatment.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3.
Fig. 4


  1. 1.

    Ellington, A.D., Szostak, J.W.: In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818–822 (1990)

    CAS  PubMed  Google Scholar 

  2. 2.

    Robertson, D.L., Joyce, G.F.: Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature 344, 467–468 (1990)

    CAS  PubMed  Google Scholar 

  3. 3.

    Tuerk, C., Gold, L.: Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505–510 (1990)

    CAS  PubMed  Google Scholar 

  4. 4.

    Kim, S.H., Thoa, T.T.T., Gu, M.B.: Aptasensors for environmental monitoring of contaminants in water and soil. Curr. Opin. Environ. Sci. Health 10, 9–21 (2019)

    Google Scholar 

  5. 5.

    Zhou, J., Rossi, J.: Aptamers as targeted therapeutics: current potential and challenges. Nat. Rev Drug Discov. 16, 181–202 (2017)

    CAS  PubMed  Google Scholar 

  6. 6.

    Stoltenburg, R., Reinemann, C., Strehlitz, B.: SELEX—a (r)evolutionary method to generate high-affinity nucleic acid ligands. Biomol. Eng. 24, 381–403 (2007)

    CAS  PubMed  Google Scholar 

  7. 7.

    Dunn, M.R., Jimenez, R.M., Chaput, J.C.: Analysis of aptamer discovery and technology. Nat. Rev. Chem. 1, 0076 (2017)

    CAS  Google Scholar 

  8. 8.

    Taylor, A.I., Holliger, P.: Directed evolution of artificial enzymes (XNAzymes) from diverse repertoires of synthetic genetic polymers. Nat. Protoc. 10, 1625–1642 (2015)

    CAS  PubMed  Google Scholar 

  9. 9.

    Kimoto, M., Yamashige, R., Matsunaga, K., Yokoyama, S., Hirao, I.: Generation of high-affinity DNA aptamers using an expanded genetic alphabet. Nat. Biotechnol. 31, 453–457 (2013)

    CAS  PubMed  Google Scholar 

  10. 10.

    Leist, M., Hartung, T.: Reprint: Inflammatory findings on species extrapolations: humans are definitely no 70-kg mice. Altex 30, 227–230 (2013)

    PubMed  Google Scholar 

  11. 11.

    Chapman, K.L., Holzgrefe, H., Black, L.E., Brown, M., Chellman, G., Copeman, C., Couch, J., Creton, S., Gehen, S., Hoberman, A., Kinter, L.B., Madden, S., Mattis, C., Stemple, H.A., Wilson, S.: Pharmaceutical toxicology: designing studies to reduce animal use, while maximizing human translation. Regul. Toxicol. Pharmacol. 66, 88–103 (2013)

    CAS  PubMed  Google Scholar 

  12. 12.

    Fielden, M.R., Kolaja, K.L.: The role of early in vivo toxicity testing in drug discovery toxicology. Expert Opin. Drug Saf. 7, 107–110 (2008)

    CAS  PubMed  Google Scholar 

  13. 13.

    Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W., Dorato, M., Deun, K.V., Smith, P., Berger, B., Heller, A.: Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul. Toxicol. Pharmacol. 32, 56–67 (2000)

    CAS  PubMed  Google Scholar 

  14. 14.

    Richardson, L., Kim, S., Menon, R., Han, A.: Organ-on-chip technology: the future of feto-maternal interface research? Front Physiol. 11, 715 (2020)

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Zhang, B., Korolj, A., Lai, B.F.L., Radisic, M.: Advances in organ-on-a-chip engineering. Nat. Rev. Mater. 3, 257–278 (2018)

    Google Scholar 

  16. 16.

    Zhang, Y., Lai, B.S., Juhas, M.: Recent advances in aptamer discovery and applications. Molecules 24, 941 (2019)

    PubMed Central  Google Scholar 

  17. 17.

    Pleiko, K., Saulite, L., Parfejevs, V., Miculis, K., Vjaters, E., Riekstina, U.: Differential binding cell-SELEX method to identify cell-specific aptamers using high-throughput sequencing. Sci. Rep. 9, 8142 (2019)

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Park, J.W., Tatavarty, R., Kim, D.W., Jung, H.T., Gu, M.B.: Immobilization-free screening of aptamers assisted by graphene oxide. Chem. Commun. (Camb) 48, 2071–2073 (2012)

    CAS  Google Scholar 

  19. 19.

    Shin, S.R., Zhang, Y.S., Kim, D.-J., Manbohi, A., Avci, H., Silvestri, A., Aleman, J., Hu, N., Kilic, T., Keung, W., Righi, M., Assawes, P., Alhadrami, H.A., Li, R.A., Dokmeci, M.R., Khademhosseini, A.: Aptamer-based microfluidic electrochemical biosensor for monitoring cell-secreted trace cardiac biomarkers. Anal. Chem. 88, 10019–10027 (2016)

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Wang, D.-L., Song, Y.-L., Zhu, Z., Li, X.-L., Zou, Y., Yang, H.-T., Wang, J.-J., Yao, P.-S., Pan, R.-J., Yang, C.J., Kang, D.-Z.: Selection of DNA aptamers against epidermal growth factor receptor with high affinity and specificity. Biochem. Biophys. Res. Commun. 453, 681–685 (2014)

    CAS  PubMed  Google Scholar 

  21. 21.

    Hung, L.Y., Wang, C.H., Hsu, K.F., Chou, C.Y., Lee, G.B.: An on-chip Cell-SELEX process for automatic selection of high-affinity aptamers specific to different histologically classified ovarian cancer cells. Lab Chip 14, 4017–4028 (2014)

    CAS  PubMed  Google Scholar 

  22. 22.

    Lee, Y.J., Kim, I.S., Park, S.-A., Kim, Y., Lee, J.E., Noh, D.-Y., Kim, K.-T., Ryu, S.H., Suh, P.-G.: Periostin-binding DNA aptamer inhibits breast cancer growth and metastasis. Mol. Ther. 21, 1004–1013 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Mendonsa, S.D., Bowser, M.T.: In vitro selection of high-affinity DNA ligands for human IgE using capillary electrophoresis. Anal. Chem. 76, 5387–5392 (2004)

    CAS  PubMed  Google Scholar 

  24. 24.

    Bompiani, K.M., Monroe, D.M., Church, F.C., Sullenger, B.A.: A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity. J. Thromb. Haemost. 10, 870–880 (2012)

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Kim, M.Y., Jeong, S.: In vitro selection of RNA aptamer and specific targeting of ErbB2 in breast cancer cells. Nucleic Acid Ther. 21, 173–178 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Mi, Z., Guo, H., Russell, M.B., Liu, Y., Sullenger, B.A., Kuo, P.C.: RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells. Mol. Ther. 17, 153–161 (2009)

    CAS  PubMed  Google Scholar 

  27. 27.

    Jellinek, D., Lynott, C.K., Rifkin, D.B., Janjić, N.: High-affinity RNA ligands to basic fibroblast growth factor inhibit receptor binding. Proc. Natl. Acad. Sci. U. S. A. 90, 11227–11231 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Stoltenburg, R., Reinemann, C., Strehlitz, B.: FluMag-SELEX as an advantageous method for DNA aptamer selection. Anal. Bioanal. Chem. 383, 83–91 (2005)

    CAS  PubMed  Google Scholar 

  29. 29.

    Huang, C.J., Lin, H.I., Shiesh, S.C., Lee, G.B.: An integrated microfluidic system for rapid screening of alpha-fetoprotein-specific aptamers. Biosens. Bioelectron. 35, 50–55 (2012)

    PubMed  Google Scholar 

  30. 30.

    Hung, L.-Y., Wang, C.-H., Che, Y.-J., Fu, C.-Y., Chang, H.-Y., Wang, K., Lee, G.-B.: Screening of aptamers specific to colorectal cancer cells and stem cells by utilizing on-chip cell-SELEX. Sci. Rep. 5, 10326 (2015)

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Ireson, C.R., Kelland, L.R.: Discovery and development of anticancer aptamers. Mol. Cancer Ther. 5, 2957–2962 (2006)

    CAS  PubMed  Google Scholar 

  32. 32.

    Onakpoya, I.J., Heneghan, C.J., Aronson, J.K.: Correction to: post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC Med. 17, 56 (2019)

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Paul, S.M., Mytelka, D.S., Dunwiddie, C.T., Persinger, C.C., Munos, B.H., Lindborg, S.R., Schacht, A.L.: How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nat. Rev. Drug Discov. 9, 203–214 (2010)

    CAS  PubMed  Google Scholar 

  34. 34.

    Vernetti, L., Gough, A., Baetz, N., Blutt, S., Broughman, J.R., Brown, J.A., Foulke-Abel, J., Hasan, N., In, J., Kelly, E., Kovbasnjuk, O., Repper, J., Senutovitch, N., Stabb, J., Yeung, C., Zachos, N.C., Donowitz, M., Estes, M., Himmelfarb, J., Truskey, G., Wikswo, J.P., Taylor, D.L.: Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Sci. Rep.. 7, 42296 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Lee, J., Choi, J.H., Kim, H.J.: Human gut-on-a-chip technology: will this revolutionize our understanding of IBD and future treatments? Expert Rev. Gastroenterol. Hepatol. 10, 883–885 (2016)

    CAS  PubMed  Google Scholar 

  36. 36.

    Ingber, D.E.: Reverse engineering human pathophysiology with organs-on-chips. Cell 164, 1105–1109 (2016)

    CAS  PubMed  Google Scholar 

  37. 37.

    Viravaidya, K., Sin, A., Shuler, M.L.: Development of a microscale cell culture analog to probe naphthalene toxicity. Biotechnol. Prog. 20, 316–323 (2004)

    CAS  PubMed  Google Scholar 

  38. 38.

    Neff, E.P.: Printing cures: organovo advances with 3D-printed liver tissue. Lab Anim (NY) 46, 57 (2017)

    Google Scholar 

  39. 39.

    Lind, J.U., Busbee, T.A., Valentine, A.D., Pasqualini, F.S., Yuan, H., Yadid, M., Park, S.-J., Kotikian, A., Nesmith, A.P., Campbell, P.H., Vlassak, J.J., Lewis, J.A., Parker, K.K.: Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing. Nat. Mater. 16, 303–308 (2017)

    CAS  PubMed  Google Scholar 

  40. 40.

    Miller, P.G., Shuler, M.L.: Design and demonstration of a pumpless 14 compartment microphysiological system. Biotechnol. Bioeng. 113, 2213–2227 (2016)

    CAS  PubMed  Google Scholar 

  41. 41.

    Ahn, S.I., Sei, Y.J., Park, H.-J., Kim, J., Ryu, Y., Choi, J.J., Sung, H.-J., MacDonald, T.J., Levey, A.I., Kim, Y.: Microengineered human blood-brain barrier platform for understanding nanoparticle transport mechanisms. Nat. Commun. 11, 175 (2020)

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Jeong, S., Kim, S., Buonocore, J., Park, J., Welsh, C.J., Li, J., Han, A.: A three-dimensional arrayed microfluidic blood-brain barrier model with integrated electrical sensor array. IEEE Trans. Biomed. Eng. 65, 431–439 (2018)

    PubMed  Google Scholar 

  43. 43.

    Sidorov, V.Y., Samson, P.C., Sidorova, T.N., Davidson, J.M., Lim, C.C., Wikswo, J.P.: I-wire heart-on-a-chip I: three-dimensional cardiac tissue constructs for physiology and pharmacology. Acta Biomater. 48, 68–78 (2017)

    CAS  PubMed  Google Scholar 

  44. 44.

    Adriani, G., Ma, D., Pavesi, A., Kamm, R.D., Goh, E.L.: A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood-brain barrier. Lab Chip 17, 448–459 (2017)

    CAS  PubMed  Google Scholar 

  45. 45.

    Huh, D., Matthews, B.D., Mammoto, A., Montoya-Zavala, M., Hsin, H.Y., Ingber, D.E.: Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010)

    CAS  PubMed  Google Scholar 

  46. 46.

    Yang, X., Li, K., Zhang, X., Liu, C., Guo, B., Wen, W., Gao, X.: Nanofiber membrane supported lung-on-a-chip microdevice for anti-cancer drug testing. Lab Chip 18, 486–495 (2018)

    CAS  PubMed  Google Scholar 

  47. 47.

    Stevens, K.R., Ungrin, M.D., Schwartz, R.E., Ng, S., Carvalho, B., Christine, K.S., Chaturvedi, R.R., Li, C.Y., Zandstra, P.W., Chen, C.S., Bhatia, S.N.: InVERT molding for scalable control of tissue microarchitecture. Nat. Commun. 4, 1847 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Spence, J.R., Mayhew, C.N., Rankin, S.A., Kuhar, M.F., Vallance, J.E., Tolle, K., Hoskins, E.E., Kalinichenko, V.V., Wells, S.I., Zorn, A.M., Shroyer, N.F., Wells, J.M.: Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105–109 (2011)

    PubMed  Google Scholar 

  49. 49.

    Chi, M., Yi, B., Oh, S., Park, D.-J., Sung, J.H., Park, S.: A microfluidic cell culture device (μFCCD) to culture epithelial cells with physiological and morphological properties that mimic those of the human intestine. Biomed. Microdevices 17, 9966 (2015)

    PubMed  Google Scholar 

  50. 50.

    Xiao, S., Coppeta, J.R., Rogers, H.B., Isenberg, B.C., Zhu, J., Olalekan, S.A., McKinnon, K.E., Dokic, D., Rashedi, A.S., Haisenleder, D.J., Malpani, S.S., Arnold-Murray, C.A., Chen, K., Jiang, M., Bai, L., Nguyen, C.T., Zhang, J., Laronda, M.M., Hope, T.J., Maniar, K.P., Pavone, M.E., Avram, M.J., Sefton, E.C., Getsios, S., Burdette, J.E., Kim, J.J., Borenstein, J.T., Woodruff, T.K.: A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle. Nat. Commun. 8, 14584 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Zhang, Y.S., Aleman, J., Shin, S.R., Kilic, T., Kim, D., Shaegh, S.A.M., Massa, S., Riahi, R., Chae, S., Hu, N., Avci, H., Zhang, W., Silvestri, A., Nezhad, A.S., Manbohi, A., Ferrari, F.D., Polini, A., Calzone, G., Shaikh, N., Alerasool, P., Budina, E., Kang, J., Bhise, N., Ribas, J., Pourmand, A., Skardal, A., Shupe, T., Bishop, C.E., Dokmeci, M.R., Atala, A., Khademhosseini, A.: Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc. Natl. Acad. Sci. U. S. A. 114, E2293-e2302 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Zavyalova, E., Samoylenkova, N., Revishchin, A., Turashev, A., Gordeychuk, I., Golovin, A., Kopylov, A., Pavlova, G.: The evaluation of pharmacodynamics and pharmacokinetics of anti-thrombin DNA Aptamer RA-36. Front Pharmacol. 8, 922 (2017)

    PubMed  PubMed Central  Google Scholar 

  53. 53.

    Sennino, B., Falcón, B.L., McCauley, D., Le, T., McCauley, T., Kurz, J.C., Haskell, A., Epstein, D.M., McDonald, D.M.: Sequential loss of tumor vessel pericytes and endothelial cells after inhibition of platelet-derived growth factor B by selective aptamer AX102. Cancer Res. 67, 7358–7367 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Akiyama, H., Kachi, S., Silva, R.L.E., Umeda, N., Hackett, S.F., McCauley, D., McCauley, T., Zoltoski, A., Epstein, D.M., Campochiaro, P.A.: Intraocular injection of an aptamer that binds PDGF-B: a potential treatment for proliferative retinopathies. J. Cell Physiol. 207, 407–412 (2006)

    CAS  PubMed  Google Scholar 

  55. 55.

    Zboralski, D., Hoehlig, K., Eulberg, D., Frömming, A., Vater, A.: Increasing tumor-infiltrating T cells through inhibition of CXCL12 with NOX-A12 synergizes with PD-1 blockade. Cancer Immunol. Res. 5, 950–956 (2017)

    CAS  PubMed  Google Scholar 

  56. 56.

    Hoellenriegel, J., Zboralski, D., Maasch, C., Rosin, N.Y., Wierda, W.G., Keating, M.J., Kruschinski, A., Burger, J.A.: The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization. Blood 123, 1032–1039 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Macdonald, J., Denoyer, D., Henri, J., Jamieson, A., Burvenich, I.J.G., Pouliot, N., Shigdar, S.: Bifunctional aptamer-doxorubicin conjugate crosses the blood-brain barrier and selectively delivers its payload to EpCAM-positive tumor cells. Nucleic Acid Ther. 30, 117–128 (2020)

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Glassman, P.M., Myerson, J.W., Ferguson, L.T., Kiseleva, R.Y., Shuvaev, V.V., Brenner, J.S., Muzykantov, V.R.: Targeting drug delivery in the vascular system: focus on endothelium. Adv. Drug Deliv. Rev. (2020)

  59. 59.

    Vinores, S.A.: Pegaptanib in the treatment of wet, age-related macular degeneration. Int. J. Nanomed. 1, 263–268 (2006)

    CAS  Google Scholar 

  60. 60.

    Mahlknecht, G., Maron, R., Mancini, M., Schechter, B., Sela, M., Yarden, Y.: Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth. Proc. Natl. Acad. Sci. U. S. A. 110, 8170–8175 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Hicke, B.J., Stephens, A.W., Gould, T., Chang, Y.-F., Lynott, C.K., Heil, J., Borkowski, S., Hilger, C.-S., Cook, G., Warren, S., Schmidt, P.G.: Tumor targeting by an aptamer. J. Nucl. Med. 47, 668–678 (2006)

    CAS  PubMed  Google Scholar 

  62. 62.

    Daniels, D.A., Chen, H., Hicke, B.J., Swiderek, K.M., Gold, L.: A tenascin-C aptamer identified by tumor cell SELEX: systematic evolution of ligands by exponential enrichment. Proc. Natl. Acad. Sci. U. S. A. 100, 15416–15421 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Hicke, B.J., Marion, C., Chang, Y.-F., Gould, T., Lynott, C.K., Parma, D., Schmidt, P.G., Warren, S.: Tenascin-C aptamers are generated using tumor cells and purified protein. J. Biol. Chem. 276, 48644–48654 (2001)

    CAS  PubMed  Google Scholar 

  64. 64.

    Talbot, L.J., Mi, Z., Bhattacharya, S.D., Kim, V., Guo, H., Kuo, P.C.: Pharmacokinetic characterization of an RNA aptamer against osteopontin and demonstration of in vivo efficacy in reversing growth of human breast cancer cells. Surgery 150, 224–230 (2011)

    PubMed  PubMed Central  Google Scholar 

  65. 65.

    Mongelard, F., Bouvet, P.: AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia. Curr. Opin. Mol. Ther. 12, 107–114 (2010)

    CAS  PubMed  Google Scholar 

  66. 66.

    Bates, P.J., Laber, D.A., Miller, D.M., Thomas, S.D., Trent, J.O.: Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp. Mol. Pathol. 86, 151–164 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Kang, S.-A., Hasan, N., Mann, A.P., Zheng, W., Zhao, L., Morris, L., Zhu, W., Zhao, Y.D., Suh, K.S., Dooley, W.C., Volk, D., Gorenstein, D.G., Cristofanilli, M., Rui, H., Tanaka, T.: Blocking the adhesion cascade at the premetastatic niche for prevention of breast cancer metastasis. Mol. Ther. 23, 1044–1054 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Mann, A.P., Somasunderam, A., Nieves-Alicea, R., Li, X., Hu, A., Sood, A.K., Ferrari, M., Gorenstein, D.G., Tanaka, T.: Identification of thioaptamer ligand against E-selectin: potential application for inflamed vasculature targeting. PLoS ONE 5, e13050 (2010)

    PubMed  PubMed Central  Google Scholar 

  69. 69.

    Roccaro, A.M., Sacco, A., Purschke, W.G., Moschetta, M., Buchner, K., Maasch, C., Zboralski, D., Zöllner, S., Vonhoff, S., Mishima, Y., Maiso, P., Reagan, M.R., Lonardi, S., Ungari, M., Facchetti, F., Eulberg, D., Kruschinski, A., Vater, A., Rossi, G., Klussmann, S., Ghobrial, I.M.: SDF-1 inhibition targets the bone marrow niche for cancer therapy. Cell Rep. 9, 118–128 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Liu, S.-C., Alomran, R., Chernikova, S.B., Lartey, F., Stafford, J., Jang, T., Merchant, M., Zboralski, D., Zöllner, S., Kruschinski, A., Klussmann, S., Recht, L., Brown, J.M.: Blockade of SDF-1 after irradiation inhibits tumor recurrences of autochthonous brain tumors in rats. Neuro Oncol. 16, 21–28 (2014)

    CAS  PubMed  Google Scholar 

  71. 71.

    McCauley, T.G., Kurz, J.C., Merlino, P.G., Lewis, S.D., Gilbert, M., Epstein, D.M., Marsh, H.N.: Pharmacologic and pharmacokinetic assessment of anti-TGFbeta2 aptamers in rabbit plasma and aqueous humor. Pharm. Res. 23, 303–311 (2006)

    CAS  PubMed  Google Scholar 

  72. 72.

    Wlotzka, B., Leva, S., Eschgfäller, B., Burmeister, J., Kleinjung, F., Kaduk, C., Muhn, P., Hess-Stumpp, H., Klussmann, S.: In vivo properties of an anti-GnRH Spiegelmer: an example of an oligonucleotide-based therapeutic substance class. Proc. Natl. Acad. Sci. U. S. A. 99, 8898–8902 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Leva, S., Lichte, A., Burmeister, J., Muhn, P., Jahnke, B., Fesser, D., Erfurth, J., Burgstaller, P., Klussmann, S.: GnRH binding RNA and DNA Spiegelmers: a novel approach toward GnRH antagonism. Chem. Biol. 9, 351–359 (2002)

    CAS  PubMed  Google Scholar 

  74. 74.

    Jellinek, D., Green, L.S., Bell, C., Janjić, N.: Inhibition of receptor binding by high-affinity RNA ligands to vascular endothelial growth factor. Biochemistry 33, 10450–10456 (1994)

    CAS  PubMed  Google Scholar 

  75. 75.

    Shangguan, D., Tang, Z., Mallikaratchy, P., Xiao, Z., Tan, W.: Optimization and modifications of aptamers selected from live cancer cell lines. ChemBioChem 8, 603–606 (2007)

    CAS  PubMed  Google Scholar 

  76. 76.

    Biesecker, G., Dihel, L., Enney, K., Bendele, R.A.: Derivation of RNA aptamer inhibitors of human complement C5. Immunopharmacology 42, 219–230 (1999)

    CAS  PubMed  Google Scholar 

  77. 77.

    Rusconi, C.P., Scardino, E., Layzer, J., Pitoc, G.A., Ortel, T.L., Monroe, D., Sullenger, B.A.: RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 419, 90–94 (2002)

    CAS  PubMed  Google Scholar 

  78. 78.

    Diener, J.L., Daniel Lagasse, H.A., Duerschmied, D., Merhi, Y., Tanguay, J.-F., Hutabarat, R., Gilbert, J., Wagner, D.D., Schaub, R.: Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779. J. Thromb. Haemost. 7, 1155–1162 (2009)

    CAS  PubMed  Google Scholar 

  79. 79.

    Buff, M.C.R., Schäfer, F., Wulffen, B., Müller, J., Pötzsch, B., Heckel, A., Mayer, G.: Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency. Nucleic Acids Res. 38, 2111–2118 (2010)

    CAS  PubMed  Google Scholar 

  80. 80.

    Waters, E.K., Genga, R.M., Schwartz, M.C., Nelson, J.A., Schaub, R.G., Olson, K.A., Kurz, J.C., McGinness, K.E.: Aptamer ARC19499 mediates a procoagulant hemostatic effect by inhibiting tissue factor pathway inhibitor. Blood 117, 5514–5522 (2011)

    CAS  PubMed  Google Scholar 

  81. 81.

    Maasch, C., Buchner, K., Eulberg, D., Vonhoff, S., Klussmann, S.: Physicochemical stability of NOX-E36, a 40mer L-RNA (Spiegelmer) for therapeutic applications. Nucleic Acids Symp. Ser. Oxf. 52, 61–62 (2008)

    CAS  Google Scholar 

  82. 82.

    Schwoebel, F., van Eijk, L.T., Zboralski, D., Sell, S., Buchner, K., Maasch, C., Purschke, W.G., Humphrey, M., Zöllner, S., Eulberg, D., Morich, F., Pickkers, P., Klussmann, S.: The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys. Blood 121, 2311–2315 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

Download references


This work was supported by the 2018 Inje University research grant.

Author information



Corresponding author

Correspondence to Sehoon Jeong.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tran, T.T.T., Delgado, A. & Jeong, S. Organ-on-a-Chip: The Future of Therapeutic Aptamer Research?. BioChip J 15, 109–122 (2021).

Download citation


  • Organ-on-a-chip
  • RNA/DNA aptamer
  • Aptamer-based organ-on-a-chip