Analysis of potential off-target effects of the therapeutic vector rAAV_U7-E53 in the treatment of Duchenne muscular dystrophy. RNASEQ_U7E53_OFFTARGET

antisense mediated exon-skipping is a therapeutic strategy aimed at restoring a functional protein in the treatment of some genetic diseases. In particular, in Duchenne muscular dystrophy, skipping of the exon 53 allow to restore a functional quasi-dystrophin. We designed a recombinant vector rAAV-U7snRNA-E53 that upon transduction into cells allow the production of an antisense sequence that will favor skipping of the DMD exon 53. Because antisense sequences can be prone to generate undesired side effects by partially hybridizing to some off-target, we designed a study to identify potential transcriptomic off-target of the therapeutic transgene U7snRNA-E53. Using RNA-Seq we seek to identify genes misregulated when it is expressed. The analysis was aimed to identify gene-level differential expression but also splicing mis-regulation.