The Scope for Thalassemia Gene Therapy by Disruption of Aberrant Regulatory Elements.

ABSTRACT: The common IVSI-110 (G>A) β-thalassemia mutation is a paradigm for intronic disease-causing mutations and their functional repair by non-homologous end joining-mediated disruption. Such mutation-specific repair by disruption of aberrant regulatory elements (DARE) is highly efficient, but to date, no systematic analysis has been performed to evaluate disease-causing mutations as therapeutic targets. Here, DARE was performed in highly characterized erythroid IVSI-110(G>A) transgenic cells and the disruption events were compared with published observations in primary CD34⁺ cells. DARE achieved the functional correction of β-globin expression equally through the removal of causative mutations and through the removal of context sequences, with disruption events and the restriction of

SUBMITTER: Patsali P 

PROVIDER: S-EPMC6912506 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature