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Morpholino oligonucleotide-mediated exon skipping for DMD treatment: Past insights, present challenges and future perspectives

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Abstract

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease primarily affecting boys causing loss of the dystrophin protein, ultimately leading to muscle wastage and death by cardiac or respiratory failure. The genetic mutation involved can be overcome with antisense oligonucleotides which bind to a pre-mRNA and results in reading frame restoration by exon skipping. Phosphorodiamidate morpholino oligonucleotides (PMOs) are a class of antisense agents with a neutral backbone derived from RNA which can induce effective exon skipping. In this review, the evolution of PMOs in exon skipping therapy for the last two decades has been detailed with the gradual structural and functional advancements. Even though the success rate of PMO-based therapy has been high with four FDA approved drugs, several key challenges are yet to overcome, one being the dystrophin restoration in cardiac muscle. The current scenario in further improvement of PMOs has been discussed along with the future perspectives that have the potential to revolutionize the therapeutic benefits in DMD.

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Acknowledgements

SS thanks SERB, New Delhi, Government of India (Grant No. TTR/2021/000044) for grant support.

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Authors and Affiliations

  1. School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700 032, India

    Shalini Gupta, Swrajit Nath Sharma & Surajit Sinha

  2. Alnylam Pharmaceuticals, Cambridge, MA, 02142, USA

    Jayanta Kundu

  3. Creyon Bio, 3210 Merryfield Row, San Diego, CA, USA

    Sankha Pattanayak

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  1. Shalini Gupta
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  2. Swrajit Nath Sharma
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Correspondence to Surajit Sinha.

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Corresponding editor: Alok Bhattacharya

This article is part of the Topical Collection: The Rare Genetic Disease Research Landscape in India.

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Gupta, S., Sharma, S.N., Kundu, J. et al. Morpholino oligonucleotide-mediated exon skipping for DMD treatment: Past insights, present challenges and future perspectives. J Biosci 48, 38 (2023). https://doi.org/10.1007/s12038-023-00365-z

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