Restoration of correct β^IVS2-654-globin mRNA splicing and HbA production by engineered U7 snRNA in β-thalassaemia/HbE erythroid cells.

ABSTRACT: A cytosine to thymine mutation at nucleotide 654 of human β-globin intron 2 (β^IVS2-654) is one of the most common mutations causing β-thalassaemia in Chinese and Southeast Asians. This mutation results in aberrant β-globin pre-mRNA splicing and prevents synthesis of β-globin protein. Splicing correction using synthetic splice-switching oligonucleotides (SSOs) has been shown to restore expression of the β-globin protein, but to maintain therapeutically relevant levels of β-globin it would require lifelong administration. Here, we demonstrate long-term splicing correction using U7 snRNA lentiviral vectors engineered to target several pre-mRNA splicing elements on the β^IVS2-654-globin pre-mRNA such as cryptic 3' splice site, aberrant 5' splice site, cryptic branch point

SUBMITTER: Nualkaew T 

PROVIDER: S-EPMC6529457 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature