Digital Droplet PCR for the Absolute Quantification of Exon Skipping Induced by Antisense Oligonucleotides in (Pre-)Clinical Development for Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a devastating, rare disease. While clinically described in the 19th century, the genetic foundation of DMD was not discovered until more than 100 years later. This genetic understanding opened the door to the development of genetic treatments for DMD. Over the course of the last 30 years, the research that supports this development has moved into the realm of clinical trials and regulatory drug approvals. Exon skipping to therapeutically restore the frame of an out-of-frame dystrophin mutation has taken center stage in drug development for DMD. The research reviewed here focuses on the clinical development of exon skipping for the treatment of DMD. In addition to the generation of clinical treatments that are being used for patient care, this research sets the stage for future therapeutic development with a focus on increasing efficacy while providing safety and addressing the multi-systemic aspects of DMD.

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Cyclic Peptides to Improve Delivery and Exon Skipping of Antisense Oligonucleotides in a Mouse Model for Duchenne Muscular Dystrophy

Molecular Therapy ◽

10.1016/j.ymthe.2017.10.004 ◽

2018 ◽

Vol 26 (1) ◽

pp. 132-147 ◽

Cited By ~ 7

Author(s):

Silvana M.G. Jirka ◽

Peter A.C. ’t Hoen ◽

Valeriano Diaz Parillas ◽

Christa L. Tanganyika-de Winter ◽

Ruurd C. Verheul ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Mouse Model ◽

Antisense Oligonucleotides ◽

Cyclic Peptides ◽

Exon Skipping

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The Pharmacokinetics of 2′-O-Methyl Phosphorothioate Antisense Oligonucleotides: Experiences from Developing Exon Skipping Therapies for Duchenne Muscular Dystrophy

Nucleic Acid Therapeutics ◽

10.1089/nat.2019.0805 ◽

2019 ◽

Vol 29 (6) ◽

pp. 305-322 ◽

Cited By ~ 3

Author(s):

Sieto Bosgra ◽

Jessica Sipkens ◽

Sjef de Kimpe ◽

Cathaline den Besten ◽

Nicole Datson ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Antisense Oligonucleotides ◽

Exon Skipping

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New Approach for Antisense Oligonucleotide-Mediated Exon Skipping in Duchenne Muscular Dystrophy

Journal of Advanced Computational Intelligence and Intelligent Informatics ◽

10.20965/jaciii.2012.p0521 ◽

2012 ◽

Vol 16 (4) ◽

pp. 521-526

Author(s):

Yoshitsugu Aoki ◽

◽

Tetsuya Nagata ◽

Shin’ichi Takeda

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Antisense Oligonucleotide ◽

Antisense Oligonucleotides ◽

Exon Skipping ◽

New Approach ◽

Reading Frame ◽

Promising Therapeutic Approach ◽

Dmd Gene ◽

Dystrophin Protein

Duchenne Muscular Dystrophy (DMD) is a lethalmuscle disorder characterized by mutations in the DMD gene. These mutations primarily disrupt the reading frame, resulting in the absence of functional dystrophin protein. Exon skipping, which involves the use of antisense oligonucleotides is a promising therapeutic approach for DMD, and clinical trials on exon skipping are currently underway in DMD patients. Recently, stable and less-toxic antisense oligonucleotides with higher efficacy have been developed in mouse and dog models of DMD. This review highlights a new approach for antisense oligonucleotide-based therapeutics for DMD, particularly for exon skipping-based methods.

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