The delivery of therapeutic sequences for the treatment of inherited genetic diseases such as Duchenne muscular dystrophy (DMD) has encountered problems such as failure to distribute beyond sites of injection and undesirable immune responses. The use of small molecules that actively affect transcription of endogenous genomic sequences has been investigated as an alternative approach to virus-delivered gene therapies and the introduction of exogenous proteins, as it offers the possibility of systemic delivery.
Antisense oligonucleotides to the boundary sequences of exon and intron 23 of the dystrophin gene in the mouse model of DMD (mdx) have previously been shown to result in successful splicing-out of the mutant exon and production of an in-frame smaller dystrophin protein in cell lines, but previous attempts to use these oligos in vivo were thwarted by apparent low levels of shortened dystrophin production. In the July 7 advanced online publication of Nature Medicine, Qi Long Lu ...
