Pharmaceuticals
Integrated Multi-Omics Identifies Valproic Acid as a Candidate for Hemophilia A
By Yujie Tang, Xin Sun, Hongyi Li and 7 others.
Abstract
Background/Objectives: Hemophilia A (HA) is caused by coagulation factor VIII (FVIII) deficiency, but its clinical heterogeneity suggests that biological alterations beyond impaired hemostasis may contribute to disease expression. This study aimed to characterize F8 knockout (F8-KO)-associated molecular changes and identify drug repositioning candidates with therapeutic potential for HA.
Methods
An F8-KO human umbilical vein endothelial cell model was generated using CRISPR/Cas9 and profiled by RNA sequencing and data-independent acquisition (DIA) proteomics. Integrated multi-omics, enrichment, and protein–protein interaction analyses informed drug repositioning using Connectivity Map (CMap), EpiMed, and DrugBank. Valproic acid (VPA) was evaluated using cell viability assays, RT-qPCR, transcriptomic profiling, and H3K27ac CUT&Tag.