A novel therapeutic strategy for β-thalassemia

In this issue of Blood, Xu et al describe a novel CRISPR/Cas approach for correcting beta-thalassemias that result from aberrant donor or acceptor splice sites. 1 The authors designed guide RNA/Cas complexes that can be introduced efficiently into hematopoietic stem and progenitor cells (HSPCs) ex vivo without viral vectors and can create double-stranded DNA cuts at specific genomic sites. The cells rapidly repair these double-stranded breaks by nonhomologous endjoining, which typically results in small deletions around the cut site. If these deletions encompass the aberrant splice sites and avoid additional sequences necessary for efficient splicing (see figure), normal splicing can be restored. [GRAPHICS] .