1 research outputs found
Bubble Liposomes and Ultrasound Exposure Improve Localized Morpholino Oligomer Delivery into the Skeletal Muscles of Dystrophic <i>mdx</i> Mice
Duchenne
muscular dystrophy (DMD) is a genetic disorder that is caused by mutations
in the DMD gene that lead to an absence of functional protein. The <i>mdx</i> dystrophic mouse contains a nonsense mutation in exon
23 of the dystrophin gene; a phosphorodiamidate morpholino oligomer
(PMO) designed to skip this mutated exon in the mRNA induces dystrophin
expression. However, an efficient PMO delivery method is needed to
improve treatment strategies for DMD. We previously developed polyethylene
glycol (PEG)-modified liposomes (Bubble liposomes) that entrap ultrasound
contrast gas and demonstrated that the combination of Bubble liposomes
with ultrasound exposure is an effective gene delivery tool <i>in vitro</i> and <i>in vivo</i>. In this study, to
evaluate the ability of Bubble liposomes as a PMO delivery tool, we
tested the potency of the Bubble liposomes combined with ultrasound
exposure to boost the delivery of PMO and increase the skipping of
the mutated exon in the <i>mdx</i> mouse. The results indicated
that the combination of Bubble liposomes and ultrasound exposure increased
the uptake of the PMO targeting a nonsense mutation in exon 23 of
the dystrophin gene and consequently increased the PMO-mediated exon-skipping
efficiency compared with PMO injection alone, leading to significantly
enhanced dystrophin expression. This increased efficiency indicated
the potential of the combination of Bubble liposomes with ultrasound
exposure to enhance PMO delivery for treating DMD. Thus, this ultrasound-mediated
Bubble liposome technique may provide an effective, noninvasive, nonviral
method for PMO therapy for DMD muscle as well as for other muscular
dystrophies