Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk.

Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk Short Title: Antisense Suppression of FXI activity in mice

THROMBOSIS AND HEMOSTASIS Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk

Existing anticoagulants effectively inhibit the activity of coagulation factors of the extrinsic and common pathway but have substantial limitations and can cause severe bleeding complications. Here we describe a novel therapeutic approach to thrombosis treatment. We have developed and characterized the efficacy and safety of selective second-generation antisense oligonucleotides (ASOs) targeti...

Antithrombotic effect of antisense factor XI oligonucleotide treatment in primates.

OBJECTIVE During coagulation, factor IX (FIX) is activated by 2 distinct mechanisms mediated by the active proteases of either FVIIa or FXIa. Both coagulation factors may contribute to thrombosis; FXI, however, plays only a limited role in the arrest of bleeding. Therefore, therapeutic targeting of FXI may produce an antithrombotic effect with relatively low hemostatic risk. APPROACH AND RESU...

Factor XI regulates pathological thrombus formation on acutely ruptured atherosclerotic plaques.

OBJECTIVE Coagulation factor XI is proposed as therapeutic target for anticoagulation. However, it is still unclear whether the antithrombotic properties of factor XI inhibitors influence atherosclerotic disease and atherothrombosis. Our aim is to investigate whether factor XI antisense oligonucleotides could prevent thrombus formation on acutely ruptured atherosclerotic plaques. APPROACH AND...

Effects of ackA, pta and poxB inhibition by antisense RNA on acetate excretion and recombinant beta interferon expression in Escherichia coli

Introduction: Escherichia coli (E.coli) is one of the most widely used hosts for the production of recombinant proteins. The main problem in getting high product yields and productivity is the accumulation of acetic acid (acetate) as an unwanted metabolic by-product. In this study, an antisense-based strategy as a metabolic engineering approach was employed to hamper the acetate excretion probl...