Exon-skipping 2.0
Tricyclo-DNA chemistry improves tissue uptake of antisense oligos to treat DMD
An emerging class of oligonucleotides appears to solve the poor tissue uptake of antisense-based therapies and produces functional recovery in preclinical studies of Duchenne muscular dystrophy. But although the tricycloDNA-based compounds could become the second generation exon-skipping oligos the field needs, they might swing the pendulum too far, and some say the problem might be to limit rather than enhance their distribution.
The reasons why the results of recent clinical studies show muted - if any - therapeutic benefit of antisense therapies in DMD aren't completely clear, but one hypothesis is that exon-skipping oligos don't induce sufficient dystrophin expression to compensate for the low levels of the protein that cause the disease. ...