Ribosomal read through as an alternative therapy for patients with hemophilia with nonsense mutations.

ABSTRACT:

Background

Drug-induced ribosomal read through can rescue nonsense mutations by inserting a replacement amino acid at the premature termination codon. Hemophilia A (HA) is well suited for this therapy as even modest increases in cofactor activity can substantially improve severe bleeding symptoms. Identifying highly efficient, low-toxicity read through compounds and pinpointing responsive mutations are critical steps in advancing this therapy.

Objectives

To compare the effects of different read through compounds and identify nonsense mutations in F8 that respond to read through treatments.

Methods

We used a cell-based model stably expressing B-domain-deleted factor (F)VIII-Gaussia luciferase fusion proteins to evaluate the efficacy of 2,6-diaminopurine (DAP), ELX-02,

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12614837 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature