Gene Editing of the Endogenous Cryptic 3' Splice Site Corrects the RNA Splicing Defect in the β⁶⁵⁴-Thalassemia Mouse Model.

ABSTRACT: β⁶⁵⁴-thalassemia is caused by a point mutation in the second intron (IVS-II) of the β-globin gene that activates a cryptic 3' splice site, leading to incorrect RNA splicing. Our previous study demonstrated that when direct deletion of the β⁶⁵⁴ mutation sequence or the cryptic 3' splice site in the IVS-II occurs, correct splicing of β-globin mRNA can be restored. Herein, we conducted an in-depth analysis to explore a more precise gene-editing method for treating β⁶⁵⁴-thalassemia. A single-base substitution of the cryptic 3' acceptor splice site was introduced in the genome of a β⁶⁵⁴-thalassemia mouse model using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9(Cas9)-mediated homology-directed repair (H

SUBMITTER: Lu D 

PROVIDER: S-EPMC11514127 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature