Better living through peptide-conjugated chemistry: Next-generation antisense oligonucleotides

Elizabeth M. McNally*, Brian D. Leverson

*Corresponding author for this work

Research output: Contribution to journalReview article

Abstract

Two different antisense oligonucleotide–based (ASO-based) therapies are currently in clinical use to treat neuromuscular diseases. This success, for Duchenne muscular dystrophy and spinal muscular atrophy, offers hope not only for additional neuromuscular diseases, but also for other disorders that could benefit from RNA-targeted therapies. A major limitation for more widespread application of ASOs relates to relatively poor tissue penetration. In this issue of the JCI, Klein et al. showed that conjugating an ASO with an arginine-rich cell-penetrating peptide, Pip6a, enhanced delivery, resulting in corrective outcome for a mouse model of myotonic dystrophy. Linking ASOs to cell-penetrating peptides, or even other moieties, is an approach currently under development with treatment potential to expand to other disorders.

Original languageEnglish (US)
Pages (from-to)4570-4571
Number of pages2
JournalJournal of Clinical Investigation
Volume129
Issue number11
DOIs
StatePublished - Nov 1 2019

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Cell-Penetrating Peptides
Neuromuscular Diseases
Antisense Oligonucleotides
Spinal Muscular Atrophy
Myotonic Dystrophy
Peptides
Duchenne Muscular Dystrophy
Arginine
RNA
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Better living through peptide-conjugated chemistry: Next-generation antisense oligonucleotides",
abstract = "Two different antisense oligonucleotide–based (ASO-based) therapies are currently in clinical use to treat neuromuscular diseases. This success, for Duchenne muscular dystrophy and spinal muscular atrophy, offers hope not only for additional neuromuscular diseases, but also for other disorders that could benefit from RNA-targeted therapies. A major limitation for more widespread application of ASOs relates to relatively poor tissue penetration. In this issue of the JCI, Klein et al. showed that conjugating an ASO with an arginine-rich cell-penetrating peptide, Pip6a, enhanced delivery, resulting in corrective outcome for a mouse model of myotonic dystrophy. Linking ASOs to cell-penetrating peptides, or even other moieties, is an approach currently under development with treatment potential to expand to other disorders.",
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Better living through peptide-conjugated chemistry : Next-generation antisense oligonucleotides. / McNally, Elizabeth M.; Leverson, Brian D.

In: Journal of Clinical Investigation, Vol. 129, No. 11, 01.11.2019, p. 4570-4571.

Research output: Contribution to journalReview article

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AU - Leverson, Brian D.

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AB - Two different antisense oligonucleotide–based (ASO-based) therapies are currently in clinical use to treat neuromuscular diseases. This success, for Duchenne muscular dystrophy and spinal muscular atrophy, offers hope not only for additional neuromuscular diseases, but also for other disorders that could benefit from RNA-targeted therapies. A major limitation for more widespread application of ASOs relates to relatively poor tissue penetration. In this issue of the JCI, Klein et al. showed that conjugating an ASO with an arginine-rich cell-penetrating peptide, Pip6a, enhanced delivery, resulting in corrective outcome for a mouse model of myotonic dystrophy. Linking ASOs to cell-penetrating peptides, or even other moieties, is an approach currently under development with treatment potential to expand to other disorders.

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