Regulatable aptamers in medicine: focus on antithrombotic strategies.
Proteins generally execute the key physiological activities required for normal growth and homeostasis. As such, many different classes of proteins, including proteases, kinases, cellular receptors and signalling proteins, represent attractive targets for diagnosis or therapy. Aptamers are small nucleic acid molecules that function as direct protein inhibitors, much like monoclonal antibodies. After a decade of intensive research, technology development and initial clinical evaluation, aptamers have now demonstrated broad potential as direct protein ligands and inhibitors, and thus represent an exciting class of compounds for the development of new therapeutic and diagnostic agents. This review will discuss the basic properties and isolation of aptamers, their use in animals and the clinic, and describe an exciting recent advance in the development of antidotes to certain aptamers, which will add a repertoire of new agents with regulatable activity for clinical use.
Duke University Medical Center, Department of Medicine, Division of Haematology, Durham, NC 27710, USA.
Anil
A
Potti
Christopher P
CP
Rusconi
Bruce A
BA
Sullenger
Thomas L
TL
Ortel
D000925:Anticoagulants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000931:Antidotes; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D052156:SELEX Aptamer Technique; D019851:Thrombophilia / Q000188:drug therapy; D013927:Thrombosis / Q000517:prevention & control
D000925:Anticoagulants; D000931:Antidotes; D052157:Aptamers, Nucleotide; D001779:Blood Coagulation Factors; D005343:Fibrinolytic Agents