Aptamer RA36 Inhibits of Human, Rabbit, and Rat Plasma Coagulation Activated with Thrombin or Snake Venom Coagulases

Abstract

RA36 DNA aptamer is a direct anticoagulant prolonging clotting time of human, rabbit, and rat plasma in the thrombin time test. Anticoagulant activity of RA36 is lower than that of recombinant hirudin. During inhibition of human plasma clotting activated with echitox (coagulase from Echis multisquamatus venom), the aptamer presumably binds to meisothrombin exosite I. The sensitivity of human plasma to the aptamer 5-fold surpasses that of rat plasma. Analysis of RA36 binding to coagulase of Agkistrodon halys venom (ancistron) is required for proving the effect of aptamer on polymerization of human fibrinogen.

Structure–Activity Relationship Study of a Potent α‐Thrombin Binding Aptamer Incorporating Hexitol Nucleotides

“…[15] Inspired by the success of HD1, a variety of novel, highly active DNA aptamers have been subsequently identified. [16][17][18][19][20] Among them, the DNA 26-mer NU172 (5ʹ-CGCCTAGGTTGGGTAGGGTGGTGGCG-3ʹ) stands as one of the latest and most representative candidates in this field. [10] NU172 displayed one of the highest binding affinities toward human αthrombin (KD = 140 pM).…”

Rapidly Neutralizable and Highly Anticoagulant Thrombin-Binding DNA Aptamer Discovered by MACE SELEX

“…Thrombin-binding aptamers (TBAs) are important in the medical and clinical fields because thrombin is a multifunctional serine protease that plays a key role in thrombosis, homeostasis, and inflammation 26 . So far, various aptamers to human α-thrombin, such as HD1, 15 HD22, 27 NU172, 28 RE31, 29 and RA36, 30 have been developed. Although HD1 and NU172 have advanced to phases I and II of clinical trials, respectively, for coronary artery bypass graft surgery, no update is available regarding the current situation 31 .…”

Applications in Which Aptamers Are Needed or Wanted in Diagnostics and Therapeutics

“…Thus, it is preferable to keep the target venom or toxin in its native three-dimensional conformation and simply develop an aptamer to bind and inhibit the venom in vitro without the need for a host animal at all, such as what the SELEX aptamer development does by obviating the need for host animals. The author and several others have had partial success with neutralizing venom degradative enzymatic activity using specifically developed aptamers [34][35][36]. The use of antivenom aptamers would be additionally advantageous to avoid serum sickness or anaphylaxis upon subsequent venomous bites, although some cytosine-phosphate-guanine (CpG)-centered sequences in aptamers are known to activate Toll-like receptors and lead to inflammation [37].…”