FKRP-related dystroglycanopathies: preclinical development of autologous cell therapy using a “universal” CRISPR / Cas9 approach

  • Exon 4 of the FKRP gene alone contains the entire coding sequence for the protein. 
  • An American team has developed a CRISPR-Cas9 approach to replace the entire exon 4 in induced pluripotent cells of patients with muscular dystrophy linked to FKRP (Walker-Warburg syndrome, congenital muscular dystrophy, LGMD R9). This allowed the restoration of a functional α-dystroglycan glycosylation both in the myotubes obtained in culture and in the corrected muscle cells transplanted into mice carrying an FKRP mutation. 
  • The functional efficacy on the muscle strength of mice still has to be demonstrated, as well as exploration of various prerequisites (production capacity, bioavailability, safety, efficacy, modes of administration, etc.) for the clinical development of such a therapeutic strategy. 


A universal gene correction approach for FKRP-associated dystroglycanopathies to enable autologous cell therapy. Dhoke NR, Kim H, Selvaraj S, Azzag K, Zhou H, Oliveira NAJ, Tungtur S, Ortiz-Cordero C, Kiley J, Lu QL, Bang AG, Perlingeiro RCR. Cell Rep. 2021 Jul 13;36(2):109360.