Rescue of a panel of Hemophilia A-causing 5'ss splicing mutations by unique Exon-specific U1snRNA variants.

ABSTRACT:

Background

Aberrant mRNA splicing is a well-established pathogenic mechanism for human disease, but its real impact is hardly predictable and underestimated. Splicing can be therefore modulated for therapeutic purposes, and splicing-switching molecules are in clinics for some diseases. Here, conscious that over 10% of all pathogenic mutations occurs at 5'ss, we aimed at characterizing and rescuing nine 5'ss mutations in three models of defective F8 exons whose skipping would lead to factor VIII (FVIII) deficiency (Hemophilia A), the most frequent coagulation factor disorder.

Methods

HEK293T cells were transfected with F8 minigene variants, alone or with engineered U1 small nuclear RNAs (U1snRNAs), and splicing patterns analysed via RT-PCR.

Results

All 5'ss mutations i

SUBMITTER: Peretto L 

PROVIDER: S-EPMC11948882 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature