A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene

Here we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice. 

We modulated the expression of Lama1 in a mouse model of MDC1A using an adeno-associated virus carrying a catalytically inactive Cas9, VP64 transactivators and single-guide RNAs that target the Lama1 promoter.

Our data demonstrated the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. This approach has a broad applicability to a variety of disease-modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.