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

Weina Ke; Morgan Chandler; Edward Cedrone; Renata F. Saito; Maria Cristina Rangel; Mara De Souza Junqueira; Jian Wang; Da Shi; Nguyen Truong; Melina Richardson; Lewis A. Rolband; Didier Dréau; Peter Bedocs; Roger Chammas; Nikolay V. Dokholyan; Marina A. Dobrovolskaia; Kirill A. Afonin

doi:10.1021/acs.nanolett.2c02019

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

Weina Ke, Morgan Chandler, Edward Cedrone, Renata F. Saito, Maria Cristina Rangel, Mara De Souza Junqueira, Jian Wang, Da Shi, Nguyen Truong, Melina Richardson, Lewis A. Rolband, Didier Dréau, Peter Bedocs, Roger Chammas, Nikolay V. Dokholyan, Marina A. Dobrovolskaia, Kirill A. Afonin

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	5961-5972
Number of pages	12
Journal	Nano letters
Volume	22
Issue number	14
DOIs	https://doi.org/10.1021/acs.nanolett.2c02019
State	Published - Jul 27 2022

All Science Journal Classification (ASJC) codes

Bioengineering
General Chemistry
General Materials Science
Condensed Matter Physics
Mechanical Engineering

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10.1021/acs.nanolett.2c02019

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Ke, W., Chandler, M., Cedrone, E., Saito, R. F., Rangel, M. C., De Souza Junqueira, M., Wang, J., Shi, D., Truong, N., Richardson, M., Rolband, L. A., Dréau, D., Bedocs, P., Chammas, R., Dokholyan, N. V., Dobrovolskaia, M. A., & Afonin, K. A. (2022). Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo. Nano letters, 22(14), 5961-5972. https://doi.org/10.1021/acs.nanolett.2c02019

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title = "Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo",

abstract = "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.",

author = "Weina Ke and Morgan Chandler and Edward Cedrone and Saito, {Renata F.} and Rangel, {Maria Cristina} and {De Souza Junqueira}, Mara and Jian Wang and Da Shi and Nguyen Truong and Melina Richardson and Rolband, {Lewis A.} and Didier Dr{\'e}au and Peter Bedocs and Roger Chammas and Dokholyan, {Nikolay V.} and Dobrovolskaia, {Marina A.} and Afonin, {Kirill A.}",

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year = "2022",

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doi = "10.1021/acs.nanolett.2c02019",

language = "English (US)",

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Ke, W, Chandler, M, Cedrone, E, Saito, RF, Rangel, MC, De Souza Junqueira, M, Wang, J, Shi, D, Truong, N, Richardson, M, Rolband, LA, Dréau, D, Bedocs, P, Chammas, R, Dokholyan, NV, Dobrovolskaia, MA & Afonin, KA 2022, 'Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo', Nano letters, vol. 22, no. 14, pp. 5961-5972. https://doi.org/10.1021/acs.nanolett.2c02019

TY - JOUR

T1 - Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo

AU - Ke, Weina

AU - Chandler, Morgan

AU - Cedrone, Edward

AU - Saito, Renata F.

AU - Rangel, Maria Cristina

AU - De Souza Junqueira, Mara

AU - Wang, Jian

AU - Shi, Da

AU - Truong, Nguyen

AU - Richardson, Melina

AU - Rolband, Lewis A.

AU - Dréau, Didier

AU - Bedocs, Peter

AU - Chammas, Roger

AU - Dokholyan, Nikolay V.

AU - Dobrovolskaia, Marina A.

AU - Afonin, Kirill A.

PY - 2022/7/27

Y1 - 2022/7/27

N2 - 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.

AB - 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.

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ER -

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

Abstract

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