Generation of an anticoagulant aptamer that targets factor V/Va and disrupts the FVa-membrane interaction in normal and COVID-19 patient samples.
Cell Chem Biol
; 29(2): 215-225.e5, 2022 02 17.
Статья
в английский
| MEDLINE | ID: covidwho-1664751
ABSTRACT
Coagulation cofactors profoundly regulate hemostasis and are appealing targets for anticoagulants. However, targeting such proteins has been challenging because they lack an active site. To address this, we isolate an RNA aptamer termed T18.3 that binds to both factor V (FV) and FVa with nanomolar affinity and demonstrates clinically relevant anticoagulant activity in both plasma and whole blood. The aptamer also shows synergy with low molecular weight heparin and delivers potent anticoagulation in plasma collected from patients with coronavirus disease 2019 (COVID-19). Moreover, the aptamer's anticoagulant activity can be rapidly and efficiently reversed using protamine sulfate, which potentially allows fine-tuning of aptamer's activity post-administration. We further show that the aptamer achieves its anticoagulant activity by abrogating FV/FVa interactions with phospholipid membranes. Our success in generating an anticoagulant aptamer targeting FV/Va demonstrates the feasibility of using cofactor-binding aptamers as therapeutic protein inhibitors and reveals an unconventional working mechanism of an aptamer by interrupting protein-membrane interactions.
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Коллекция:
Международные базы данных
база данных:
MEDLINE
Основная тема:
Blood Coagulation
/
Factor V
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Factor Va
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Aptamers, Nucleotide
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Anticoagulants
Тип исследования:
Прогностическое исследование
/
Систематический обзор/метаанализ
Язык:
английский
Журнал:
Cell Chem Biol
Год:
2022
Тип:
Статья
Аффилированная страна:
J.chembiol.2022.01.009
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