Oligonucleotide-mediated gene therapy for muscular dystrophies.

摘要

Several new approaches to gene therapy for the muscular dystrophies involve oligonucleotides as targeting vectors. These oligonucleotides are designed to repair genetic mutations, to modify genomic sequences in order to compensate for gene deletions, or to modify RNA processing in order to ameliorate the effects of the underlying gene mutation. Among the various approaches currently under investigation for dystrophin mutations that cause Duchenne muscular dystrophy is the use of chimeric RNA/DNA oligonucleotides ("chimeraplasts") to repair point mutations. Studies in the mdx mouse and the GRMD dog have demonstrated that point mutations in the dystrophin gene can be corrected by chimeraplasts that have been injected into muscles. The scope of this review includes a summary of the current status of chimeraplast-mediated gene repair for dystrophin mutations, ongoing studies to apply chimeraplast-mediated gene repair to frame-shift deletions of the dystrophin gene, and major hurdles that need to be overcome to translate current experimental successes into a viable therapeutic modality for Duchenne muscular dystrophy.