Skip to main content
Log in

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

  • Review Article
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

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, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3.
Fig. 4

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  PubMed  PubMed Central  Google Scholar 

  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)

    Article  Google Scholar 

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

    Article  PubMed Central  Google Scholar 

  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)

    Article  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  PubMed  Google Scholar 

  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)

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  PubMed  Google Scholar 

  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)

    Article  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. 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)

    Article  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  PubMed  PubMed Central  Google Scholar 

  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. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  Google Scholar 

  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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sehoon Jeong.

Rights and permissions

Reprints and permissions

About this article

Check for updates. 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). https://doi.org/10.1007/s13206-021-00016-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-021-00016-1

Keywords

Navigation