Evaluation of warfarin resistance using transcription activator-like effector nucleases-mediated vitamin K epoxide reductase knockout HEK293 cells.

ABSTRACT:

Background

Single nucleotide polymorphisms in the vitamin K epoxide reductase (VKOR) gene have been successfully used for warfarin dosage prediction. However, warfarin resistance studies of naturally occurring VKOR mutants do not correlate with their clinical phenotype. This discrepancy presumably arises because the in vitro VKOR activity assay is performed under artificial conditions using the non-physiological reductant dithiothreitol.

Objectives

The aim of this study is to establish an in vivo VKOR activity assay in mammalian cells (HEK293) where VKOR functions in its native milieu without interference from endogenous enzymes.

Methods

Endogenous VKOR activity in HEK293 cells was knocked out by transcription activator-like effector nucleases (TALENs)-mediated genome

SUBMITTER: Tie JK 

PROVIDER: S-EPMC3745541 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature