CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells.

The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases.

The acquisition of relative clauses by Tamil children.

This paper reports the findings of a cross-sectional study that investigated the acquisition of relative clauses by 27 Tamil-speaking children, who ranged in age from 2;11 to 6;6. A picture-cued production task was used to elicit relative clauses from the child subjects. An analysis of the subjects' responses revealed that children below the age of 5;0 relativized significantly less often than the older children; furthermore, when they did produce relative clauses, they exhibited a strong preference for the tag relative and produced significantly fewer participial relatives than the older children. The findings also indicated that the younger children produced a significantly greater number of pragmatically inappropriate responses than the older children. It is argued that the observed age-related differences in Tamil children's relativizations very likely stem from performance factors and that the younger children are probably not inferior to the older children with respect to their grammatical and pragmatic competence.