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Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

Gunaratne R, Kumar S, Frederiksen JW, Stayrook S, Lohrmann JL, Perry K, Bompiani KM, Chabata CV, Thalji NK, Ho MD, Arepally G, Camire RM, Krishnaswamy S, Sullenger BA
Nat Biotechnol 36 606-613 (2018)
Cited: 30 times
EuropePMC logo PMID: 29863725

Abstract

Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the activity of an alternative anticoagulant, the RNA aptamer 11F7t, we solved X-ray crystal structures of the aptamer bound to factor Xa (FXa). The finding that 11F7t did not bind the catalytic site suggested that it could complement small-molecule FXa inhibitors. We demonstrate that combinations of 11F7t and catalytic-site FXa inhibitors enhance anticoagulation in purified reaction mixtures and plasma. Aptamer-drug combinations prevented clot formation as effectively as UFH in human blood circulated in an extracorporeal oxygenator circuit that mimicked CPB, while avoiding side effects of UFH. An antidote could promptly neutralize the anticoagulant effects of both FXa inhibitors. Our results suggest that drugs and aptamers with shared targets can be combined to exert more specific and potent effects than either agent alone.

Reviews - 5voe mentioned but not cited (1)

  1. Structural Biology for the Molecular Insight between Aptamers and Target Proteins. Zhang N, Chen Z, Liu D, Jiang H, Zhang ZK, Lu A, Zhang BT, Yu Y, Zhang G. Int J Mol Sci 22 4093 (2021)

Articles - 5voe mentioned but not cited (3)

  1. Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass. Gunaratne R, Kumar S, Frederiksen JW, Stayrook S, Lohrmann JL, Perry K, Bompiani KM, Chabata CV, Thalji NK, Ho MD, Arepally G, Camire RM, Krishnaswamy S, Sullenger BA. Nat Biotechnol 36 606-613 (2018)
  2. Predicting aptamer sequences that interact with target proteins using an aptamer-protein interaction classifier and a Monte Carlo tree search approach. Lee G, Jang GH, Kang HY, Song G. PLoS One 16 e0253760 (2021)
  3. Investigating RNA-protein recognition mechanisms through supervised molecular dynamics (SuMD) simulations. Pavan M, Bassani D, Sturlese M, Moro S. NAR Genom Bioinform 4 lqac088 (2022)


Reviews citing this publication (7)

  1. A review of lipidation in the development of advanced protein and peptide therapeutics. Menacho-Melgar R, Decker JS, Hennigan JN, Lynch MD. J Control Release 295 1-12 (2019)
  2. Overview of the Therapeutic Potential of Aptamers Targeting Coagulation Factors. Liu M, Zaman K, Fortenberry YM. Int J Mol Sci 22 3897 (2021)
  3. A Mini-Review: Clinical Development and Potential of Aptamers for Thrombotic Events Treatment and Monitoring. Ponce AT, Hong KL. Biomedicines 7 E55 (2019)
  4. Recent Progress on Highly Selective and Sensitive Electrochemical Aptamer-based Sensors. Tang T, Liu Y, Jiang Y. Chem Res Chin Univ 38 866-878 (2022)
  5. Targeting DAMPs with nucleic acid scavengers to treat lupus. Olson LB, Hunter NI, Rempel RE, Sullenger BA. Transl Res 245 30-40 (2022)
  6. Aptamers Regulating the Hemostasis System. Vaganov AA, Taranushenko TE, Luzan NA, Shchugoreva IA, Kolovskaya OS, Artyushenko PV, Zamay TN, Kichkailo AS. Molecules 27 8593 (2022)
  7. Structural Insights into Protein-Aptamer Recognitions Emerged from Experimental and Computational Studies. Troisi R, Balasco N, Autiero I, Vitagliano L, Sica F. Int J Mol Sci 24 16318 (2023)

Articles citing this publication (19)

  1. Preclinical Development of a vWF Aptamer to Limit Thrombosis and Engender Arterial Recanalization of Occluded Vessels. Nimjee SM, Dornbos D, Pitoc GA, Wheeler DG, Layzer JM, Venetos N, Huttinger A, Talentino SE, Musgrave NJ, Moody H, Rempel RE, Jones C, Carlisle K, Wilson J, Bratton C, Joseph ME, Khan S, Hoffman MR, Sommerville L, Becker RC, Zweier JL, Sullenger BA. Mol Ther 27 1228-1241 (2019)
  2. A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis. Zhao S, Tian R, Wu J, Liu S, Wang Y, Wen M, Shang Y, Liu Q, Li Y, Guo Y, Wang Z, Wang T, Zhao Y, Zhao H, Cao H, Su Y, Sun J, Jiang Q, Ding B. Nat Commun 12 358 (2021)
  3. Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers. Moreno A, Pitoc GA, Ganson NJ, Layzer JM, Hershfield MS, Tarantal AF, Sullenger BA. Cell Chem Biol 26 634-644.e3 (2019)
  4. Machine learning guided aptamer refinement and discovery. Bashir A, Yang Q, Wang J, Hoyer S, Chou W, McLean C, Davis G, Gong Q, Armstrong Z, Jang J, Kang H, Pawlosky A, Scott A, Dahl GE, Berndl M, Dimon M, Ferguson BS. Nat Commun 12 2366 (2021)
  5. An Aptamer for Broad Cancer Targeting and Therapy. Powell Gray B, Song X, Hsu DS, Kratschmer C, Levy M, Barry AP, Sullenger BA. Cancers (Basel) 12 E3217 (2020)
  6. Aptamers as Reversible Sorting Ligands for Preparation of Cells in Their Native State. Gray BP, Requena MD, Nichols MD, Sullenger BA. Cell Chem Biol 27 232-244.e7 (2020)
  7. Bioinspired liquid gating membrane-based catheter with anticoagulation and positionally drug release properties. Wang C, Wang S, Pan H, Min L, Zheng H, Zhu H, Liu G, Yang W, Chen X, Hou X. Sci Adv 6 eabb4700 (2020)
  8. Structural basis of prostate-specific membrane antigen recognition by the A9g RNA aptamer. Ptacek J, Zhang D, Qiu L, Kruspe S, Motlova L, Kolenko P, Novakova Z, Shubham S, Havlinova B, Baranova P, Chen SJ, Zou X, Giangrande P, Barinka C. Nucleic Acids Res 48 11130-11145 (2020)
  9. Aptamer-based factor IXa inhibition preserves hemostasis and prevents thrombosis in a piglet model of ECMO. Reed CR, Bonadonna D, Otto JC, McDaniel CG, Chabata CV, Kuchibhatla M, Frederiksen J, Layzer JM, Arepally GM, Sullenger BA, Tracy ET. Mol Ther Nucleic Acids 27 524-534 (2022)
  10. Exosite binding drives substrate affinity for the activation of coagulation factor X by the intrinsic Xase complex. Basavaraj MG, Krishnaswamy S. J Biol Chem 295 15198-15207 (2020)
  11. Generation of an anticoagulant aptamer that targets factor V/Va and disrupts the FVa-membrane interaction in normal and COVID-19 patient samples. Soule EE, Yu H, Olson L, Naqvi I, Kumar S, Krishnaswamy S, Sullenger BA. Cell Chem Biol 29 215-225.e5 (2022)
  12. Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in Cardiopulmonary Bypass and COVID-19. Chabata CV, Frederiksen JW, Olson LB, Naqvi IA, Hall SE, Gunaratne R, Kraft BD, Que LG, Chen L, Sullenger BA. Nucleic Acid Ther 32 139-150 (2022)
  13. Pharmacokinetic, Hemostatic, and Anticancer Properties of a Low-Anticoagulant Bovine Heparin. Santos RP, Tovar AMF, Oliveira MR, Piquet AA, Capillé NV, Oliveira SNMCG, Correia AH, Farias JN, Vilanova E, Mourão PAS. TH Open 6 e114-e123 (2022)
  14. Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes. Gray BP, Kelly L, Steen-Burrell KA, Layzer JM, Rempel RE, Nimjee SM, Cooley BC, Tarantal AF, Sullenger BA. Mol Ther Nucleic Acids 31 440-451 (2023)
  15. Spatial imaging of glycoRNA in single cells with ARPLA. Ma Y, Guo W, Mou Q, Shao X, Lyu M, Garcia V, Kong L, Lewis W, Ward C, Yang Z, Pan X, Yi SS, Lu Y. Nat Biotechnol (2023)
  16. Applications and future of aptamers that achieve rapid-onset anticoagulation. Yu H, Frederiksen J, Sullenger BA. RNA 29 455-462 (2023)
  17. Approaches to Assure Similarity between Pharmaceutical Heparins from Two Different Manufacturers. Bezerra FF, Oliveira SNMCG, Sales RA, Piquet AA, Capillé NV, Vilanova E, Tovar AMF, Mourão PAS. Pharmaceutics 15 1115 (2023)
  18. New insight into the traditional model of the coagulation cascade and its regulation: illustrated review of a three-dimensional view. Troisi R, Balasco N, Autiero I, Sica F, Vitagliano L. Res Pract Thromb Haemost 7 102160 (2023)
  19. Protocol for purification of cells in their native state using reversible aptamer-antidote pairs. Requena MD, Gray BP, Sullenger BA. STAR Protoc 4 102348 (2023)


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