Exon Skipping Therapy
نویسندگان
چکیده
Exondys 51 is the first therapy for Duchenne muscular dystrophy (DMD) to have been granted accelerated approval by the FDA. Approval was granted based on using dystrophin expression as a surrogate marker. Exondys 51 targets DMD exon 51 for skipping to restore the reading frame for 13% of Duchenne patients.
منابع مشابه
Exon skipping for nonsense mutations in Duchenne muscular dystrophy: too many mutations, too few patients?
INTRODUCTION Duchenne muscular dystrophy (DMD), one of the most common and lethal genetic disorders, is caused by mutations of the dystrophin gene. Removal of an exon or of multiple exons using antisense molecules has been demonstrated to allow synthesis of truncated 'Becker muscular dystrophy-like' dystrophin. AREAS COVERED Approximately 15% of DMD cases are caused by a nonsense mutation. Al...
متن کاملEffective Exon Skipping and Dystrophin Restoration by 2′-O-Methoxyethyl Antisense Oligonucleotide in Dystrophin-Deficient Mice
Antisense oligonucleotide (AO)-mediated exon-skipping therapy is one of the most promising therapeutic strategies for Duchenne Muscular Dystrophy (DMD) and several AO chemistries have been rigorously investigated. In this report, we focused on the effect of 2'-O-methoxyethyl oligonucleotides (MOE) on exon skipping in cultured mdx myoblasts and mice. Efficient dose-dependent skipping of targeted...
متن کاملSystemic Antisense Therapeutics for Dystrophin and Myostatin Exon Splice Modulation Improve Muscle Pathology of Adult mdx Mice
Antisense-mediated exon skipping is a promising approach for the treatment of Duchenne muscular dystrophy (DMD), a rare life-threatening genetic disease due to dystrophin deficiency. Such an approach can restore the disrupted reading frame of dystrophin pre-mRNA, generating a truncated form of the protein. Alternatively, antisense therapy can be used to induce destructive exon skipping of myost...
متن کاملMulti-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is one of the most common lethal genetic diseases worldwide, caused by mutations in the dystrophin (DMD) gene. Exon skipping employs short DNA/RNA-like molecules called antisense oligonucleotides (AONs) that restore the reading frame and produce shorter but functional proteins. However, exon skipping therapy faces two major hurdles: limited applicability (up to...
متن کاملEvaluation of anhydrohexitol nucleic acid, cyclohexenyl nucleic acid and d-altritol nucleic acid-modified 2'-O-methyl RNA mixmer antisense oligonucleotides for exon skipping in vitro.
Antisense oligonucleotide (AO) mediated exon skipping has been widely explored as a therapeutic strategy for several diseases, in particular, for rare genetic disorders such as Duchenne muscular dystrophy (DMD). To date, the potential of anhydrohexitol nucleic acid (HNA), cyclohexenyl nucleic acid (CeNA) and altritol nucleic acid (ANA) has not been explored in exon skipping. For the first time,...
متن کاملPhosphorothioate modification of chimeric 2´-O-methyl RNA/ethylene-bridged nucleic acid oligonucleotides increases dystrophin exon 45 skipping capability and reduces cytotoxicity.
BACKGROUNDS Antisense oligonucleotide (AO)-mediated exon skipping is the most promising way to express internally deleted dystrophin in Duchenne muscular dystrophy (DMD), by correcting the reading frame of dystrophin mRNA. An antisense chimeric oligonucleotide consisting of 2´-O-methyl RNA and ethylene-bridged nucleic acid (ENA), targeting exon 45 of the dystrophin gene, AO85, has been shown to...
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ورودعنوان ژورنال:
- Cell
دوره 167 شماره
صفحات -
تاریخ انتشار 2016