DMD – ANIMAL MODELS & PRECLINICAL TREATMENT: P.213 Absence of toxicity with intravenous dosing of the Exon 2-skipping AAV9.U7-ACCA vector in non-human primates

Abstract

Therapeutic exon skipping as a treatment for Duchenne muscular dystrophy (DMD) has largely concentrated on delivery of antisense oligomers to treat out-of-frame exon deletions. Here we report on the preclinical development of an AAV9 vector containing four copies of the non-coding U7 small nuclear RNA (U7snRNA), each targeted to either the splice donor or the splice acceptor sites of DMD exon 2. We have previously shown that delivery of this vector (rAAV9.U7.ACCA) to the Dup2 mouse model results in expression of full-length dystrophin from wild-type DMD mRNA, as well as an IRES-driven isoform translated only in the absence of exon 2 (Del2 mRNA).