7 Aptamers for Personalized Therapeutics
193
Aptamers for Antithrombotic Therapy
Thromboses are considered as major determinants of mortality in the elderly people.
Heparin acts as an anticoagulant by interacting with plasma protein antithrombin
and increases its activity against blood-clotting factors IIa (thrombin), IXa, and Xa.
Moreover, heparin therapy against thromboses was considered to increase the risk of
continuous bleeding, and consequently faced the risk of thromboses without treatment and risk of bleeding due to treatment. A novel strategy of therapeutics was
planned to specifically target a selective coagulation protein. So far, several RNA
aptamers with Kd from 0.4 to 13 nM against factor IXa (FXIa) were reported along
with their diverse mechanisms such as interfering with factor XII, anionic binding,
and disrupting tissue factor VII(a) complex assembly. Among these, reversible RNA
aptamer antagonists (9.3t) bound to factor XIa with a Kd of 0.58 nM that exhibited
greater than 5000-fold specificity for FXIa compared with the structurally similar
coagulation factors VIIa, Xa, and XIa, and activated protein C. With respect to
DNA aptamers, only two have been described to date. The ssDNA ligand 60–
18 inhibited thrombin-catalyzed fibrin clot formation with a Kd of approximately
0.5 nM. The second designated aptamer strongly bound factor XIa with Kd of 1.8 nM
competitively inhibited factor XIa complex formation with antithrombin [93–95].
Aptamers Against Obesity, Diabetes mellitus, and Multiple Sclerosis
The differentiation of white adipocytes is related to excessive deposited energy in
body which leads to obesity. MA-33 and 91 aptamers were selected against mature
adipocytes cells 3T3-L1 with Kd of 143 and 33 nM but not bound with preadipocytes
[96]. A correlation between low glucose production in diabetes mellitus with inhibition of glucagon receptor (GCGR) activity was reported. Based on this information Wang et al. reported a GCGR DNA aptamer antagonist GR-3 which bound to
membrane protein of CHOGCGR cells with a Kd of 53 nM [97]. Occurrence of
multiple sclerosis (MS) is represented by the presence of proteolytic autoantibodies
against myelin basic protein. A high affinity RNA aptamer 2–9 having Kd value 15 nm
was reported, which could bound to proteolytic antimyelin basic protein autoantibodies from MS patients. Covalent conjugate of the aptamer and Ca21-regulated
photoproteinobelin were further developed into a bioluminescent microplate sensor
to detect target antibodies [98].
193
Aptamers for Antithrombotic Therapy
Thromboses are considered as major determinants of mortality in the elderly people.
Heparin acts as an anticoagulant by interacting with plasma protein antithrombin
and increases its activity against blood-clotting factors IIa (thrombin), IXa, and Xa.
Moreover, heparin therapy against thromboses was considered to increase the risk of
continuous bleeding, and consequently faced the risk of thromboses without treatment and risk of bleeding due to treatment. A novel strategy of therapeutics was
planned to specifically target a selective coagulation protein. So far, several RNA
aptamers with Kd from 0.4 to 13 nM against factor IXa (FXIa) were reported along
with their diverse mechanisms such as interfering with factor XII, anionic binding,
and disrupting tissue factor VII(a) complex assembly. Among these, reversible RNA
aptamer antagonists (9.3t) bound to factor XIa with a Kd of 0.58 nM that exhibited
greater than 5000-fold specificity for FXIa compared with the structurally similar
coagulation factors VIIa, Xa, and XIa, and activated protein C. With respect to
DNA aptamers, only two have been described to date. The ssDNA ligand 60–
18 inhibited thrombin-catalyzed fibrin clot formation with a Kd of approximately
0.5 nM. The second designated aptamer strongly bound factor XIa with Kd of 1.8 nM
competitively inhibited factor XIa complex formation with antithrombin [93–95].
Aptamers Against Obesity, Diabetes mellitus, and Multiple Sclerosis
The differentiation of white adipocytes is related to excessive deposited energy in
body which leads to obesity. MA-33 and 91 aptamers were selected against mature
adipocytes cells 3T3-L1 with Kd of 143 and 33 nM but not bound with preadipocytes
[96]. A correlation between low glucose production in diabetes mellitus with inhibition of glucagon receptor (GCGR) activity was reported. Based on this information Wang et al. reported a GCGR DNA aptamer antagonist GR-3 which bound to
membrane protein of CHOGCGR cells with a Kd of 53 nM [97]. Occurrence of
multiple sclerosis (MS) is represented by the presence of proteolytic autoantibodies
against myelin basic protein. A high affinity RNA aptamer 2–9 having Kd value 15 nm
was reported, which could bound to proteolytic antimyelin basic protein autoantibodies from MS patients. Covalent conjugate of the aptamer and Ca21-regulated
photoproteinobelin were further developed into a bioluminescent microplate sensor
to detect target antibodies [98].