Limited efficacy of using AAV-U7 to deliver antisense oligonucleotides to the brains of DMD mouse models

Researchers at the University of Versailles-Saint-Quentin tested antisense oligonucleotides (ASOs) targeting exonPartie codante de l’ADN au sein d’un gène. 51 skipping of the DMD gene in mdx52 mice, models of Duchenne muscular dystrophy (DMD) with exon 52 deletion, thereby disrupting dystrophin (Dp427) expression in the brain:

• previous work by the same researchers had shown that these ASOs were truly effective in targeting the central nervous system when injected alone via the local-regional route,
• the addition of an AAV-U7 system, designed to increase their local production, did not achieve the expected result, despite using the same intracerebral administration routes and targeting exon 51 of the DMD gene,
• regardless of the capsid chosen for the AAV« adeno-associated virus » , ou virus adéno-associé est un petit virus à ADN simple brin. Il fait partie de la famille des Parvoviridae et appartient au genre des Dependovirus. La particule virale est constituée d’un brin d’ADN de polarité positive ou négative protégé par une capside. La taille moyenne d’une particule d’AAV et de 18 à 22 nm. Les AAV sont les seuls parvovirus non autonomes. Lorsqu’on emploie « rAAV » , il s’agit du virus AAV recombinant, c’est-à-dire qu’il a été modifié pour devenir un vecteur (et n’est donc plus virulent)..

Even though this approach with AAV-U7 allows for real, but modest, re-expression of dystrophin in the brain, the clinical effect is inconclusive in this animal.

Ineffective behavioral rescue despite partial brain Dp427 restoration by AAV9-U7-mediated exon 51 skipping in mdx52 mice. Vacca O, Saoudi A, Doisy M et al. Mol Ther Nucleic Acids. 2025 Nov