Comparative analysis of antisense oligonucleotide sequences targeting exon 53 of the human DMD gene: Implications for future clinical trials

Antisense-mediated modulation of splicing: Therapeutic implications for Duchenne muscular dystrophy

“…This mouse model has been used to confirm the efficacy of 2OMePS, PMO AONs and of AAV delivered U7 snRNPs targeting human exon 51, to directly compare 2OMePS and PMOs and recently in a comparative study to identify an optimal PMO targeting exon 53. 34,38,62,65,66 Since exon skipping that restored the open reading frame in patients, disrupts the open reading frame in unaffected individuals, the exon skipping approach cannot be tested in healthy volunteers (Fig. 2).…”

Genetic Therapy for Duchenne Muscular Dystrophy: Principles and Progress

“…There are a number of alternative peptide conjugates that show promise as enhancers of deliverability and are undergoing rapid pre-clinical development (Yin et al, 2010). The next planned UK phase I trial by the MDEX consortium will involve conjugation of a PPMO developed for the targeted skipping of exon 53 (Popplewell et al, 2010) and is supported by a Wellcome Trust. The Dutch are currently performing a phase I trial using a 2'OMe PS AON for the targeted skipping of exon 45.…”

Optimal classification for the diagnosis of duchenne muscular dystrophy images using support vector machines

“…The nonsense mutations in the DMD (approximately 2.4 Mb) gene always induce exon skipping and thus result in the absence of or defect in the dystrophin [4]. According to that, antisense-mediated exon skipping therapies such as antisense oligonucleotides are the more promising therapeutic schemes to skip additional exons that border the deletions in human DMD gene [5,6]. Moreover, evidences have evaluated the effectiveness of recombinant adeno-associated virus (AAV) vectors and chimeric AAV capsid variant on the therapy for DMD animal models due to their potential to arrest or reverse muscle failure [2,7,8].…”