Chapter 10
Aptamers for Thrombotic Diseases
Weibin Li, Shenghang Zhang, Meng Zhao, and Xiaopeng Lan
Abstract Thrombosis is defined as a necessary physiological clotting process of
hemostasis or harmful clinical events manifested as acute myocardial infarction
(AMI), acute coronary syndromes (ACS), and thrombotic diseases. Nowadays,
thrombotic diseases are the leading causes of morbidity and mortality which incur
substantial healthcare expenditures worldwide. There are some shortcomings for
current antithrombotics including bleeding potential, unpredictable pharmacokinetic
and pharmacodynamic profiles, limited reversibility, and so on. Aptamers are short
RNA or single-stranded DNA (ssDNA) oligonucleotides that fold into 3D conformations to recognize and bind their cognate targets. Aptamers are selected by an
in vitro selection technique, i.e., Systematic Evolution of Ligands by Exponential
Enrichment (SELEX). Chemical synthesis renders aptamers both the characteristics
of small molecule drugs and those of monoclonal antibodies. Some additional unique
features, such as high specificity and affinity, flexible modification and stability, and
lack of toxicity and immunogenicity, make aptamers hold great potential as a novel
class of drugs and diagnostic reagents. In this review, we focus on the development
of several aptamers and in particular those aptamers that have entered into clinical
trials against anticoagulation factors and anti-adhesion molecules which are potential
antithrombotics for thrombotic diseases.
10.1 Introduction
The coagulation process is a major player in maintaining body hemostasis. It is a
series of chemical bio-transformations that comprise the intrinsic pathway, extrinsic
pathway, and common pathways. The coagulation factors of the intrinsic pathway
include VIII, IX, XI, XII, prekallikrein (PK), and high-molecular-weight kininogen
(HMWK) as well as phospholipids and Ca
2+ ions. The extrinsic pathway involves
tissue factor (TF) and coagulation factors VII (FVII), and coagulation factors of
W. Li · S. Zhang · M. Zhao · X. Lan (B)
Institute for Laboratory Medicine, The 900th Hospital of Joint Logistic Support Force, PLA, No.
156 North Xi-er Huan Road, Fuzhou 350025, Fujian, China
e-mail: lanxp@sina.com
© Springer Nature Singapore Pte Ltd. 2021
Y. Dong (ed.), Aptamers for Medical Applications,
https://doi.org/10.1007/978-981-33-4838-7_10
279
Aptamers for Thrombotic Diseases
Weibin Li, Shenghang Zhang, Meng Zhao, and Xiaopeng Lan
Abstract Thrombosis is defined as a necessary physiological clotting process of
hemostasis or harmful clinical events manifested as acute myocardial infarction
(AMI), acute coronary syndromes (ACS), and thrombotic diseases. Nowadays,
thrombotic diseases are the leading causes of morbidity and mortality which incur
substantial healthcare expenditures worldwide. There are some shortcomings for
current antithrombotics including bleeding potential, unpredictable pharmacokinetic
and pharmacodynamic profiles, limited reversibility, and so on. Aptamers are short
RNA or single-stranded DNA (ssDNA) oligonucleotides that fold into 3D conformations to recognize and bind their cognate targets. Aptamers are selected by an
in vitro selection technique, i.e., Systematic Evolution of Ligands by Exponential
Enrichment (SELEX). Chemical synthesis renders aptamers both the characteristics
of small molecule drugs and those of monoclonal antibodies. Some additional unique
features, such as high specificity and affinity, flexible modification and stability, and
lack of toxicity and immunogenicity, make aptamers hold great potential as a novel
class of drugs and diagnostic reagents. In this review, we focus on the development
of several aptamers and in particular those aptamers that have entered into clinical
trials against anticoagulation factors and anti-adhesion molecules which are potential
antithrombotics for thrombotic diseases.
10.1 Introduction
The coagulation process is a major player in maintaining body hemostasis. It is a
series of chemical bio-transformations that comprise the intrinsic pathway, extrinsic
pathway, and common pathways. The coagulation factors of the intrinsic pathway
include VIII, IX, XI, XII, prekallikrein (PK), and high-molecular-weight kininogen
(HMWK) as well as phospholipids and Ca
2+ ions. The extrinsic pathway involves
tissue factor (TF) and coagulation factors VII (FVII), and coagulation factors of
W. Li · S. Zhang · M. Zhao · X. Lan (B)
Institute for Laboratory Medicine, The 900th Hospital of Joint Logistic Support Force, PLA, No.
156 North Xi-er Huan Road, Fuzhou 350025, Fujian, China
e-mail: lanxp@sina.com
© Springer Nature Singapore Pte Ltd. 2021
Y. Dong (ed.), Aptamers for Medical Applications,
https://doi.org/10.1007/978-981-33-4838-7_10
279