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

L.J. Popplewell; C. Adkin; V. Arechavala-Gomeza; A. Aartsma-Rus; C.L. de Winter; S.D. Wilton; J.E. Morgan; F. Muntoni; I.R. Graham; G. Dickson

doi:10.1016/j.nmd.2009.10.013

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

Journal article

Peer reviewed

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

L.J. Popplewell, C. Adkin, V. Arechavala-Gomeza, A. Aartsma-Rus, C.L. de Winter, S.D. Wilton, J.E. Morgan, F. Muntoni, I.R. Graham and G. Dickson

Neuromuscular Disorders, Vol.20(2), pp.102-110

2010

DOI: https://doi.org/10.1016/j.nmd.2009.10.013

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Abstract

Duchenne muscular dystrophy (DMD) is caused by the lack of functional dystrophin protein, most commonly as a result of a range of out-of-frame mutations in the DMD gene. Modulation of pre-mRNA splicing with antisense oligonucleotides (AOs) to restore the reading frame has been demonstrated in vitro and in vivo, such that truncated but functional dystrophin is expressed. AO-induced skipping of exon 51 of the DMD gene, which could treat 13% of DMD patients, has now progressed to clinical trials. We describe here the methodical, cooperative comparison, in vitro (in DMD cells) and in vivo (in a transgenic mouse expressing human dystrophin), of 24 AOs of the phosphorodiamidate morpholino oligomer (PMO) chemistry designed to target exon 53 of the DMD gene, skipping of which could be potentially applicable to 8% of patients. A number of the PMOs tested should be considered worthy of development for clinical trial.

Details

Title: Comparative analysis of antisense oligonucleotide sequences targeting exon 53 of the human DMD gene: Implications for future clinical trials
Authors/Creators: L.J. Popplewell (Author/Creator)
C. Adkin (Author/Creator)
V. Arechavala-Gomeza (Author/Creator)
A. Aartsma-Rus (Author/Creator)
C.L. de Winter (Author/Creator)
S.D. Wilton (Author/Creator)
J.E. Morgan (Author/Creator)
F. Muntoni (Author/Creator)
I.R. Graham (Author/Creator)
G. Dickson (Author/Creator)
Publication Details: Neuromuscular Disorders, Vol.20(2), pp.102-110
Publisher: Elsevier BV
Identifiers: 991005541832107891
Copyright: 2009 Elsevier B.V.
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.255 Musculoskeletal Disorders; 1.255.628 Duchenne Muscular Dystrophy
Web Of Science research areas: Clinical Neurology; Neurosciences
ESI research areas: Neuroscience & Behavior