Phosphorodiamidate morpholino oligomers (PMOs; figure 1) are non-toxic, and in the mdx mouse model of DMD they were the most effective oligomer chemistry for inducing exon skipping and restoring long-lasting (weeks) dystrophin expression after intravenous or intramuscular injection.2124 PMOs, unlike other antisense oligonucleotides, are uncharged, not metabolised, and in preclinical or clinical studies were not associated with activation of the immune system, anaphylaxis, hypotension, or anti-arrhythmias.25 On the basis of these data, we have studied the safety and biochemical efficacy of AVI-4658, a PMO designed to target exon 51 that is delivered by intramuscular injection.
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