Multiplex Profiling of miR-122 for Preclinical and Clinical Evaluation of Drug-Induced Liver Injury by a Full-Scale Platform.

Abstract

Diagnostic and monitoring for drug-induced liver injury (DILI) predominantly rely on serum aminotransferases. However, owing to their widespread expression across multiple organs, a significant challenge emerges from the absence of reliable biomarkers for DILI diagnosis. Herein, we introduce a concept for DILI detection, circumventing the nonspecific elevation and delayed release of aminotransferases and then straightforwardly focusing on the core feature of DILI, abnormal gene expression caused by drug overdose. The developed full-scale platform integrates the properties of spherical nucleic acids with elaborately designed fluorescence <i>in situ</i> hybridization sequences, enabling the sensitive and specific profiling of drug-overdosed miR-122 expression alterations across molecular, cellular, organismal, and clinical scales and effectively bypassing the phenotypic features of disease. Furthermore, the diagnostic efficacies of serum and total RNA extracted from both mouse and human blood samples for DILI diagnosis were analyzed using the receiver operating characteristic curve and principal component analysis. We anticipate that this universal platform holds potential in facilitating DILI diagnosis, therapeutic evaluation, and prognosis.