TY - JOUR
T1 - Better living through peptide-conjugated chemistry
T2 - Next-generation antisense oligonucleotides
AU - McNally, Elizabeth M.
AU - Leverson, Brian D.
N1 - Funding Information:
Conflict of interest: EMM is a coauthor on patents for multiexon skipping (US Patents 9777271 and 10273483). EMM founded Ikaika Therapeutics, received grant support from Solid Biosciences, and consulted for Exonics, Invitae, AstraZeneca, Tenaya Therapeutics, 4D Molecular Therapeutics, and Cytokinetics. Copyright: © 2019, American Society for Clinical Investigation. Reference information: J Clin Invest. 2019;129(11):4570–4571. https://doi.org/10.1172/JCI131933.
Funding Information:
EMM and BDL are supported by NIH grants HL128075, AR052646, and HL061322.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
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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U2 - 10.1172/JCI131933
DO - 10.1172/JCI131933
M3 - Review article
C2 - 31566581
AN - SCOPUS:85074378583
VL - 129
SP - 4570
EP - 4571
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 11
ER -