Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo

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Citações na Scopus
7
Tipo de produção
article
Data de publicação
2022
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMERICAN CHEMICAL SOCIETY
Autores
KE, W.
CHANDLER, M.
CEDRONE, E.
WANG, J.
SHI, D.
TRUONG, N.
RICHARDSON, M.
Citação
NANO LETTERS, v.22, n.14, p.5961-5972, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a ""kill-switch""mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in vivo in comparison to free aptamers. Finally, we confirm the efficacy of the ""kill-switch""mechanism in vivo in murine and porcine models.
Palavras-chave
anticoagulation, aptamers, immunoquiescent, in vivo, kill-switch, RNA-DNA fibers
Referências
  1. Esmon C.T., Xu J., Lupu F., Innate immunity and coagulation, J. Thromb Haemost, 9, pp. 182-188, (2011)
  2. Prandoni P., Falanga A., Piccioli A., Cancer, thrombosis and heparin-induced thrombocytopenia, Thromb Res., 120, pp. S137-S140, (2007)
  3. Ten Cate H., Falanga A., Overview of the postulated mechanisms linking cancer and thrombosis, Pathophysiol Haemost Thromb, 36, 34, pp. 122-130, (2009)
  4. MacKman N., Bergmeier W., Stouffer G.A., Weitz J.I., Therapeutic strategies for thrombosis: new targets and approaches, Nat. Rev. Drug Discovery, 19, 5, pp. 333-352, (2020)
  5. Kushner A., West W.P., Pillarisetty L.S., Virchow Triad, (2022)
  6. Araya S., Mamo M.A., Tsegay Y.G., Atlaw A., Aytenew A., Hordofa A., Negeso A.E., Wordofa M., Niguse T., Cheru M., Tamir Z., Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia, PLoS One, 16, 6, (2021)
  7. Rajabto W., Priantono D., Mulyadi R., Pulmonary Embolism in Hospitalized Patient with Coronavirus Disease 2019 (COVID-19), Acta Med. Indones, 53, 4, pp. 493-496, (2021)
  8. Cook B.W., Anticoagulation management, Semin Intervent Radiol, 27, 4, pp. 360-367, (2010)
  9. Nutescu E.A., Burnett A., Fanikos J., Spinler S., Wittkowsky A., Pharmacology of anticoagulants used in the treatment of venous thromboembolism, J. Thromb. Thrombolysis, 41, 1, pp. 15-31, (2016)
  10. Hong E., Halman J.R., Shah A., Cedrone E., Truong N., Afonin K.A., Dobrovolskaia M.A., Toll-like receptor-mediated recognition of nucleic acid nanoparticles (NANPs) in human primary blood cells, Molecules, 24, 6, (2019)
  11. Panigaj M., Johnson M.B., Ke W., McMillan J., Goncharova E.A., Chandler M., Afonin K.A., Aptamers as modular components of therapeutic nucleic acid nanotechnology, ACS Nano, 13, 11, pp. 12301-12321, (2019)
  12. Johnson M.B., Chandler M., Afonin K.A., Nucleic acid nanoparticles (NANPs) as molecular tools to direct desirable and avoid undesirable immunological effects, Adv. Drug Deliv Rev., 173, pp. 427-438, (2021)
  13. Bouchard P.R., Hutabarat R.M., Thompson K.M., Discovery and development of therapeutic aptamers, Annu. Rev. Pharmacol Toxicol, 50, pp. 237-257, (2010)
  14. Woodruff R.S., Sullenger B.A., Modulation of the coagulation cascade using aptamers, Arterioscler Thromb Vasc Biol., 35, 10, pp. 2083-2091, (2015)
  15. Chan M.Y., Cohen M.G., Dyke C.K., Myles S.K., Aberle L.G., Lin M., Walder J., Steinhubl S.R., Gilchrist I.C., Kleiman N.S., Vorchheimer D.A., Chronos N., Melloni C., Alexander J.H., Harrington R.A., Tonkens R.M., Becker R.C., Rusconi C.P., Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease, Circulation, 117, 22, pp. 2865-2874, (2008)
  16. Chan M.Y., Rusconi C.P., Alexander J.H., Tonkens R.M., Harrington R.A., Becker R.C., A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor, J. Thromb Haemost, 6, 5, pp. 789-796, (2008)
  17. Dyke C.K., Steinhubl S.R., Kleiman N.S., Cannon R.O., Aberle L.G., Lin M., Myles S.K., Melloni C., Harrington R.A., Alexander J.H., Becker R.C., Rusconi C.P., First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity, Circulation, 114, 23, pp. 2490-2497, (2006)
  18. Krissanaprasit A., Key C.M., Froehlich K., Pontula S., Mihalko E., Dupont D.M., Andersen E.S., Kjems J., Brown A.C., LaBean T.H., Multivalent aptamer-functionalized single-strand RNA origami as effective, target-specific anticoagulants with corresponding reversal agents, Adv. Healthc Mater., 10, 11, (2021)
  19. 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, 6902, pp. 90-94, (2002)
  20. 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., A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis, Nat. Commun., 12, 1, (2021)
  21. Rusconi C.P., Roberts J.D., Pitoc G.A., Nimjee S.M., White R.R., Quick G., Scardino E., Fay W.P., Sullenger B.A., Antidote-mediated control of an anticoagulant aptamer in vivo, Nat. Biotechnol., 22, 11, pp. 1423-1428, (2004)
  22. Rangnekar A., Zhang A.M., Li S.S., Bompiani K.M., Hansen M.N., Gothelf K.V., Sullenger B.A., LaBean T.H., Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures, Nanomedicine-Nanotechnology Biology and Medicine, 8, 5, pp. 673-681, (2012)
  23. Raber M.N., Walker H.K., Hall W.D., Hurst J.W., Coagulation Tests, Clinical Methods: The History, Physical, and Laboratory Examinations, (1990)
  24. De Cristofaro R., De Candia E., Thrombin domains: Structure, function and interaction with platelet receptors, J. Thromb. Thrombolysis, 15, 3, pp. 151-163, (2003)
  25. Di Cera E., Thrombin, Mol. Aspects Med., 29, 4, pp. 203-254, (2008)
  26. Bock L.C., Griffin L.C., Latham J.A., Vermaas E.H., Toole J.J., Selection of single-stranded DNA molecules that bind and inhibit human thrombin, Nature, 355, 6360, pp. 564-566, (1992)
  27. Kretz C.A., Stafford A.R., Fredenburgh J.C., Weitz J.I., HD1, a thrombin-directed aptamer, binds exosite 1 on prothrombin with high affinity and inhibits its activation by prothrombinase, J. Biol. Chem., 281, 49, pp. 37477-37485, (2006)
  28. Mayer G., Rohrbach F., Potzsch B., Muller J., Aptamer-based modulation of blood coagulation, Hamostaseologie, 31, 4, pp. 258-263, (2011)
  29. Zavyalova E., Golovin A., Reshetnikov R., Mudrik N., Panteleyev D., Pavlova G., Kopylov A., Novel modular DNA aptamer for human thrombin with high anticoagulant activity, Curr. Med. Chem., 18, 22, pp. 3343-3350, (2011)
  30. 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, Frontiers in Pharmacology, 8, (2017)
  31. Roxo C., Kotkowiak W., Pasternak A., G-Quadruplex-Forming Aptamers-Characteristics, Applications, and Perspectives, Molecules, 24, 20, (2019)
  32. Zavyalova E., Golovin A., Pavlova G., Kopylov A., Module-Activity Relationship of G-quadruplex Based DNA Aptamers for Human Thrombin, Curr. Med. Chem., 20, 38, pp. 4836-4843, (2013)
  33. Zavyalova E., Samoylenkova N., Revishchin A., Golovin A., Pavlova G., Kopylov A., Evaluation of Antithrombotic Activity of Thrombin DNA Aptamers by a Murine Thrombosis Model, PLoS One, 9, 9, (2014)
  34. Becker R.C., Povsic T., Cohen M.G., Rusconi C.P., Sullenger B., Nucleic acid aptamers as antithrombotic agents: Opportunities in extracellular therapeutics, Thromb Haemost, 103, 3, pp. 586-595, (2010)
  35. Ke W., Hong E., Saito R.F., Rangel M.C., Wang J., Viard M., Richardson M., Khisamutdinov E.F., Panigaj M., Dokholyan N.V., Chammas R., Dobrovolskaia M.A., Afonin K.A., RNA-DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-kappaB in human cells, Nucleic Acids Res., 47, 3, pp. 1350-1361, (2019)
  36. Palta S., Saroa R., Palta A., Overview of the coagulation system, Indian J. Anaesth, 58, 5, pp. 515-523, (2014)
  37. Henry S.P., Jagels M.A., Hugli T.E., Manalili S., Geary R.S., Giclas P.C., Levin A.A., Mechanism of alternative complement pathway dysregulation by a phosphorothioate oligonucleotide in monkey and human serum, Nucleic Acid Ther, 24, 5, pp. 326-335, (2014)
  38. Paz S., Hsiao J., Cauntay P., Soriano A., Bai L., MacHemer T., Xiao X., Guo S., Hung G., Younis H., Bennett C.F., Henry S., Yun T.J., Burel S., The Distinct and Cooperative Roles of Toll-Like Receptor 9 and Receptor for Advanced Glycation End Products in Modulating In Vivo Inflammatory Responses to Select CpG and Non-CpG Oligonucleotides, Nucleic Acid Ther, 27, 5, pp. 272-284, (2017)
  39. Ilinskaya A.N., Shah A., Enciso A.E., Chan K.C., Kaczmarczyk J.A., Blonder J., Simanek E.E., Dobrovolskaia M.A., Nanoparticle physicochemical properties determine the activation of intracellular complement, Nanomedicine: Nanotechnology, Biology and Medicine, 17, pp. 266-275, (2019)
  40. Janeway C.A., Travers P., Walport M., Shlomchik M.J., The complement system and innate immunity, Immunobiology: The Immune System in Health and Disease, (2001)
  41. Vogel C.W., Fritzinger D.C., Hew B.E., Thorne M., Bammert H., Recombinant cobra venom factor, Molecular Immunology, 41, 23, pp. 191-199, (2004)
  42. Janovec V., Hodek J., Clarova K., Hofman T., Dostalik P., Fronek J., Chlupac J., Chaperot L., Durand S., Baumert T.F., Pichova I., Lubyova B., Hirsch I., Weber J., Toll-like receptor dual-acting agonists are potent inducers of PBMC-produced cytokines that inhibit hepatitis B virus production in primary human hepatocytes, Sci. Rep, 10, 1, (2020)
  43. Tahtinen S., Tong A.J., Himmels P., Oh J., Paler-Martinez A., Kim L., Wichner S., Oei Y., McCarron M.J., Freund E.C., Amir Z.A., De La Cruz C.C., Haley B., Blanchette C., Schartner J.M., Ye W., Yadav M., Sahin U., Delamarre L., Mellman I., IL-1 and IL-1ra are key regulators of the inflammatory response to RNA vaccines, Nat. Immunol, 23, 4, pp. 532-542, (2022)
  44. Franzese O., Palermo B., Di Donna C., Sperduti I., Ferraresi V., Stabile H., Gismondi A., Santoni A., Nistico P., Polyfunctional Melan-A-specific tumor-reactive CD8(+) T cells elicited by dacarbazine treatment before peptide-vaccination depends on AKT activation sustained by ICOS, Oncoimmunology, 5, 5, (2016)
  45. Hong E., Halman J.R., Shah A.B., Khisamutdinov E.F., Dobrovolskaia M.A., Afonin K.A., Structure and Composition Define Immunorecognition of Nucleic Acid Nanoparticles, Nano Lett., 18, 7, pp. 4309-4321, (2018)
  46. Markiewski M.M., Lambris J.D., The role of complement in inflammatory diseases from behind the scenes into the spotlight, Am. J. Pathol., 171, 3, pp. 715-727, (2007)
  47. Guo J.W., Gao X.L., Su L.N., Xia H.M., Gu G.Z., Pang Z.Q., Jiang X.G., Yao L., Chen J., Chen H.Z., Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery, Biomaterials, 32, 31, pp. 8010-8020, (2011)
  48. Kryza D., Debordeaux F., Azema L., Hassan A., Paurelle O., Schulz J., Savona-Baron C., Charignon E., Bonazza P., Taleb J., Fernandez P., Janier M., Toulme J.J., Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas, PLoS One, 11, 2, (2016)
  49. Healy J.M., Lewis S.D., Kurz M., Boomer R.M., Thompson K.M., Wilson C., McCauley T.G., Pharmacokinetics and biodistribution of novel aptamer compositions, Pharm. Res-Dordr, 21, 12, pp. 2234-2246, (2004)
  50. Liu Y., Jennings N.L., Dart A.M., Du X.J., Standardizing a simpler, more sensitive and accurate tail bleeding assay in mice, World J. Exp Med., 2, 2, pp. 30-36, (2012)
  51. Russell W.M.S., Burch R.L., The Principles of Humane Experimental Technique, (1959)
  52. Sashindranath M., Sturgeon S.A., French S., Craenmehr D.D.D., Selan C., Freddi S., Johnson C., Cody S.H., Nesbitt W.S., Hamilton J.R., Nandurkar H.H., The mode of anesthesia influences outcome in mouse models of arterial thrombosis, Res. Pract Thromb Haemost, 3, 2, pp. 197-206, (2019)
  53. Pollack C.V., Reilly P.A., Eikelboom J., Glund S., Verhamme P., Bernstein R.A., Dubiel R., Huisman M.V., Hylek E.M., Kamphuisen P.W., Et al., Idarucizumab for dabigatran reversal, New England Journal of Medicine, 373, 6, pp. 511-520, (2015)