Human NR1I3 adenoviral particles

The NR1I3 gene is located on human chromosome 1q23.3 and encodes the constitutive androstane receptor (CAR), also commonly referred to as the pregnane X receptor (PXR). It belongs to the nuclear receptor superfamily (NR1 subfamily, group I, member 3) and functions as a ligand-activated transcription factor. CAR/PXR primarily forms heterodimers with retinoid X receptor α (RXRα) and binds to specific response elements (e.g., PBREM, DR-3, DR-4 motifs) in the regulatory regions of target genes. Its primary physiological role is as a master regulator of the detoxification and elimination of xenobiotics and endogenous substances. CAR/PXR is able to sense an extremely wide range of ligands, including prescription drugs, environmental pollutants, bile acids, steroid hormones, and certain vitamins. Upon activation, it regulates the transcriptional upregulation of a large number of genes encoding phase I drug metabolizing enzymes (particularly CYP2B6, CYP2C9, CYP3A4), phase II conjugating enzymes (e.g., UGT1A1, SULTs), and phase III drug transporters (e.g., MDR1/P-gp, MRP2). This critical role makes CAR/PXR a crucial player in drug interactions, inter-individual variability in drug response, bile acid homeostasis, energy metabolism, and potentially cancer progression and chemoresistance.

Human NR1I3 adenoviral particles are specially designed recombinant viral vectors that deliver and express the human NR1I3 (CAR/PXR) gene to a variety of mammalian cell types in vivo and in vitro. These viral particles are based on modified human adenoviruses, typically adenovirus type 5 (Ad5), which are rendered replication-incompetent by deleting essential early genes (E1 and E3 regions). They are valuable tools for studying CAR/PXR function, including ligand screening, target gene identification, signaling pathway studies, exploring their roles in drug metabolism, toxicity, and disease mechanisms (e.g., cholestasis, fatty liver, cancer), and potentially for gene therapy approaches.