A potent anti-coagulant RNA aptamer inhibits blood coagulation by specifically blocking the extrinsic clotting pathway

被引:50
作者
Gopinath, Subash C. B.
Shikamoto, Yasuo
Mizuno, Hiroshi
Kumar, Penmetcha K. R.
机构
[1] Natl Inst Adv Ind Sci & Technol AIST Cent 6, Inst Biol Resources & Funct, Funct Nucle Acids Grp, Tsukuba, Ibaraki 3058566, Japan
[2] Natl Inst Adv Ind Sci & Technol, Agr Dimens Res Ctr, Tsukuba, Ibaraki 3058566, Japan
[3] NEC Soft Co Ltd, VALWAY Technol Ctr, Tokyo, Japan
关键词
aptamer; blood coagulation; extrinsic and intrinsic pathway; inhibition; RNA;
D O I
10.1160/TH06-01-0047
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A potent antidote-controlled aptamer, as an anticoagulant, has reportedly overcome the complications of acute bleeding by the administration of available anticoagulants. In the present study, we provide evidence that the aptamer binds specifically to factors IX and IXa and inhibits their functions. Furthermore,we demonstrated that the aptamer inhibits blood coagulation by interfering with the extrinsic pathway, blocking the complex of factor VIIa and tissue factor interactions with factor IX The results from the previous and present studies suggest that the aptamer probably binds in the vicinity of the EGF1 and EGF2 domains of factor IX.
引用
收藏
页码:767 / 771
页数:5
相关论文
共 12 条
[1]   Nucleic acid aptamers in therapeutic anticoagulation - Technology, development and clinical application [J].
Becker, RC ;
Rusconi, C ;
Sullenger, B .
THROMBOSIS AND HAEMOSTASIS, 2005, 93 (06) :1014-1020
[2]  
Chen SWW, 2002, THROMB HAEMOSTASIS, V88, P74
[3]   Guide to anticoagulant therapy: Heparin a statement for healthcare professionals from the American Heart Association [J].
Hirsh, J ;
Anand, SS ;
Halperin, JL ;
Fuster, V .
CIRCULATION, 2001, 103 (24) :2994-3018
[4]   PROTEOLYTIC ACTIVATION OF HUMAN FACTOR-IX AND FACTOR-X BY RECOMBINANT HUMAN FACTOR-VIIA - EFFECTS OF CALCIUM, PHOSPHOLIPIDS, AND TISSUE FACTOR [J].
KOMIYAMA, Y ;
PEDERSEN, AH ;
KISIEL, W .
BIOCHEMISTRY, 1990, 29 (40) :9418-9425
[5]   Aptamers: An emerging class of therapeutics [J].
Nimjee, SM ;
Rusconi, CP ;
Sullenger, BA .
ANNUAL REVIEW OF MEDICINE, 2005, 56 :555-+
[6]   The potential of aptamers as anticoagulants [J].
Nirnjee, SM ;
Rusconi, CP ;
Harrington, RA ;
Sullenger, BA .
TRENDS IN CARDIOVASCULAR MEDICINE, 2005, 15 (01) :41-45
[7]   Antidote-mediated control of an anticoagulant aptamer in vivo [J].
Rusconi, CP ;
Roberts, JD ;
Pitoc, GA ;
Nimjee, SM ;
White, RR ;
Quick, G ;
Scardino, E ;
Fay, WP ;
Sullenger, BA .
NATURE BIOTECHNOLOGY, 2004, 22 (11) :1423-1428
[8]   RNA aptamers as reversible antagonists of coagulation factor IXa [J].
Rusconi, CP ;
Scardino, E ;
Layzer, J ;
Pitoc, GA ;
Ortel, TL ;
Monroe, D ;
Sullenger, BA .
NATURE, 2002, 419 (6902) :90-94
[9]   Structure-function relationships in factor IX and factor IXa [J].
Schmidt, AE ;
Bajaj, SP .
TRENDS IN CARDIOVASCULAR MEDICINE, 2003, 13 (01) :39-45
[10]   RNA aptamers as pathway-specific MAP kinase inhibitors [J].
Seiwert, SD ;
Nahreini, TS ;
Aigner, S ;
Ahn, NG ;
Uhlenbeck, OC .
CHEMISTRY & BIOLOGY, 2000, 7 (11) :833-843