Gao QQ, Wyatt E, Goldstein JA, LoPresti P, Castillo LM, Gazda A, Petrossian N, Earley JU, Hadhazy M, Barefield DY, Demonbreun AR, Bönnemann C, Wolf M, McNally EM. Reengineering a transmembrane protein to treat muscular dystrophy using exon skipping. J Clin Invest. 2015 Nov 2;125(11):4186-95. PMID: 26457733; PMCID: PMC4639981.
From the abstract: "Exon skipping uses antisense oligonucleotides as a treatment for genetic diseases. ... Exon skipping is currently being tested in humans with dystrophin gene mutations who have Duchenne muscular dystrophy. ... We generated an internally truncated γ-sarcoglycan protein that we have termed Mini-Gamma by deleting a large portion of the extracellular domain. Mini-Gamma provided functional and pathological benefits to correct the loss of γ-sarcoglycan in a Drosophila model, in heterologous cell expression studies, and in transgenic mice lacking γ-sarcoglycan. We generated a cellular model of human muscle disease and showed that multiple exon skipping could be induced in RNA that encodes a mutant human γ-sarcoglycan. Since Mini-Gamma represents removal of 4 of the 7 coding exons in γ-sarcoglycan, this approach provides a viable strategy to treat the majority of patients with γ-sarcoglycan gene mutations."