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W. Li et al.
molecule therapeutics. Like antibodies, aptamers bind and block the target surface
by folding into a tertiary 3D structure that is structurally complementary to the target
with high binding affinity [49, 50]. Aptamers are similar to small molecule therapeutics in several aspects, for example, easily chemical synthesis and modification
or conjugation, lack of immunogenicity and toxicity. Additionally, aptamers can be
delivered with drug molecules, liposomes, micelle, PEG, and nanomaterials [134,
135] to the vascular compartment through intravenous or subcutaneous administration and to different tissues [18]. Aptamer-antidote anticoagulant pairs may represent
an ideal strategy for the management of thrombotic disorders and conditions requiring
either short-term or graded antithrombotic therapy. Moreover, aptamers could serve
as probes and imaging molecules for illustrating the thrombosis pathology [3].
During the past two decades, several aptamers against coagulation factors and
adhesion molecules have been developed and entered into clinical trials for cardiovascular diseases. The above-mentioned data indicated these aptamers reduced bleeding
risk compared to present antiplatelet agents or anticoagulants. However, antithrombotic aptamers are still at their infancy with less experience, and there are still
some major hurdles for widespread use of aptamer therapeutics. Firstly, the selection process of aptamer is labor-intensive, time-consuming, and a low success rate,
more efficient SELEX protocols like mirror-image and Toggle SELEX protocol are
needed to develop more effective aptamers. Secondly, effective chemical modification and conjugates as well as delivery systems are required for aptamer therapeutics
to resist serum nuclease degradation, renal secretion, and liver metabolism. Thirdly,
oral bioavailability is a challenge for aptamers for long-term antiplatelet therapy in
thrombotic diseases [9].
However, many pharmaceutical companies, for example, Archemix & Nuvelo,
ARCA Biopharma, and Noxxon Pharma AG have contributed to the development
of aptamer drugs. Among them, the Archemix Corporation holds the majority of
intellectual property (IP) rights of aptamers including the exclusive rights to conduct
the SELEX process to develop aptamers, and patents on composition and administration of aptamer agents [4, 136]. With the development of the SELEX technique and further progress of both preclinical and clinical trials, the development
of aptamer-based therapeutics will speed up and aptamers will be promising alternatives or additive therapeutics of traditional antithrombotics in treating thrombotic
diseases [9].
Acknowledgement Special thanks to my father, Ke-Chang Li, who was commander of the 85 th
division of land force of PLA. He taught me integrity, kind-hearted and trustworthiness. February 13
in 2020, I went to Wuhan with military medical unit the next day after he accepted radical resection
of rectal carcinoma, and I lost him forever in 40 days when I was fighting the COVID-19 epidemic
in Taikang-Tongji hospital in Wuhan. Nowadays, I am deeply cherishing the memory when I was
walking with my father in those of golden sunset. He was a handsome gentleman with silver hair
and I am always happy beside him like a baby girl. In addition, I want to express my gratitude
to Professor Yi-Yang Dong and Lian-Ming Liao, they encouraged me to finish the writing when I
immersed myself in sadness.
W. Li et al.
molecule therapeutics. Like antibodies, aptamers bind and block the target surface
by folding into a tertiary 3D structure that is structurally complementary to the target
with high binding affinity [49, 50]. Aptamers are similar to small molecule therapeutics in several aspects, for example, easily chemical synthesis and modification
or conjugation, lack of immunogenicity and toxicity. Additionally, aptamers can be
delivered with drug molecules, liposomes, micelle, PEG, and nanomaterials [134,
135] to the vascular compartment through intravenous or subcutaneous administration and to different tissues [18]. Aptamer-antidote anticoagulant pairs may represent
an ideal strategy for the management of thrombotic disorders and conditions requiring
either short-term or graded antithrombotic therapy. Moreover, aptamers could serve
as probes and imaging molecules for illustrating the thrombosis pathology [3].
During the past two decades, several aptamers against coagulation factors and
adhesion molecules have been developed and entered into clinical trials for cardiovascular diseases. The above-mentioned data indicated these aptamers reduced bleeding
risk compared to present antiplatelet agents or anticoagulants. However, antithrombotic aptamers are still at their infancy with less experience, and there are still
some major hurdles for widespread use of aptamer therapeutics. Firstly, the selection process of aptamer is labor-intensive, time-consuming, and a low success rate,
more efficient SELEX protocols like mirror-image and Toggle SELEX protocol are
needed to develop more effective aptamers. Secondly, effective chemical modification and conjugates as well as delivery systems are required for aptamer therapeutics
to resist serum nuclease degradation, renal secretion, and liver metabolism. Thirdly,
oral bioavailability is a challenge for aptamers for long-term antiplatelet therapy in
thrombotic diseases [9].
However, many pharmaceutical companies, for example, Archemix & Nuvelo,
ARCA Biopharma, and Noxxon Pharma AG have contributed to the development
of aptamer drugs. Among them, the Archemix Corporation holds the majority of
intellectual property (IP) rights of aptamers including the exclusive rights to conduct
the SELEX process to develop aptamers, and patents on composition and administration of aptamer agents [4, 136]. With the development of the SELEX technique and further progress of both preclinical and clinical trials, the development
of aptamer-based therapeutics will speed up and aptamers will be promising alternatives or additive therapeutics of traditional antithrombotics in treating thrombotic
diseases [9].
Acknowledgement Special thanks to my father, Ke-Chang Li, who was commander of the 85 th
division of land force of PLA. He taught me integrity, kind-hearted and trustworthiness. February 13
in 2020, I went to Wuhan with military medical unit the next day after he accepted radical resection
of rectal carcinoma, and I lost him forever in 40 days when I was fighting the COVID-19 epidemic
in Taikang-Tongji hospital in Wuhan. Nowadays, I am deeply cherishing the memory when I was
walking with my father in those of golden sunset. He was a handsome gentleman with silver hair
and I am always happy beside him like a baby girl. In addition, I want to express my gratitude
to Professor Yi-Yang Dong and Lian-Ming Liao, they encouraged me to finish the writing when I
immersed myself in sadness.