A A Review on the Potential of Application of CRISPR/Cas9 Technology in CYP3A4 and CYP2D6 Genes: A Way to Move Forward in Identifying New Drug Targets

Abstract

The cytochrome P450 (CYP) enzymes are of a ubiquitous heme–thiolate proteins family that plays an important role within the biotransformation of endogenous molecules and xenobiotics as today’s market is bio-transformed through CYP-mediated metabolism. Major CYP isoforms involved in most reactions are mainly CYP3A4 and CYP2D6. The CYP3A4 is found most extensively within the human liver and gut in which this CYP-isoform takes part in the phase I transformation of toxins, carcinogens, bile acids, and steroid hormones while CYP2D6 plays a central role in the oxidative metabolism of up to 25% of drugs in common clinical use, although it only accounts for 1-5% of the CYP liver content. With the help of vast gene editing technologies such as the CRISPR/Cas9 system, researchers have found its application to be useful and efficient in gene knockout studies involving genetic variants in association with drug metabolism due to its simplicity and affordability. Hence, this review aims to explore the potential use of CRISPR/Cas9 technology in gene editing in vitro studies particularly in knocking out the gene of interest, mainly drug metabolism enzymes. This article will explore how CRISPR/cas9 facilitates ex vivo assays of drug metabolism studies. The long-term goal for bio-editing is an in vivo treatment without the risk of causing harm to humans and providing a ready-to-be-used drug metabolism assay for ex vivo studies of drug development and pharmacokinetics study at a lower cost.