A Genetic Intervention Stands a Skip Away from Clinical Tests

摘要

Establishing dystrophin as the mutated gene in Duchenne muscular dystrophy (DMD) was arguably the first successful use of genetic information to identify a human disease gene (1). Despite the large investment in the Human Genome Project in the ensuing quarter-century, few therapies have been developed for genetic disorders. Fortunately, this is starting to change for DMD, a condition characterized by loss of functional muscle fibers and progressive muscle weakness and deterioration. Multiple therapies, including gene therapy, gene up-regulation, and transcript modification, are in various stages of clinical trials for the disease. One promising approach uses antisense oli-gonucleotides to induce a process called exon skipping in precursor mRNA (pre-mRNA), and has advanced to phase II clinical trials (2,3). However, results thus far are below the threshold needed for the therapy to be effective. Kendall et al. now report a class of drugs that increases the efficiency of exon skipping (4). This could prove critical to achieving therapeutic benefit and increases the prospects for using antisense oligonucleotides as a treatment for DMD.