Site-directed mutagenesis of tissue factor pathway inhibitor-binding exosite D60A on factor VII results in a new factor VII variant with lower coagulant activity.

ABSTRACT:

Background

Recombinant factor (F)VIIa (rFVIIa) has been approved by the US Food and Drug Administration for the treatment of hemophilia A and B with inhibitors and congenital FVII deficiency. Moreover, the investigational uses of rFVIIa are becoming of interest since it can be used to treat various clinical bleeding conditions. However, there is evidence showing that rFVIIa is a potent procoagulant agent that potentially leads to an increased risk of thrombotic complications.

Objectives

To design a new rFVII with lower coagulant activity that could potentially be used as an alternative hemostatic agent aiming to minimize the risk of thrombogenicity.

Methods

D60A was introduced into the F7 sequence by polymerase chain reaction-based mutagenesis. Wild type (WT) a

SUBMITTER: Seanoon K 

PROVIDER: S-EPMC10840347 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature