ArticleProceedings of the National Academy of Sciences of the United States of America2016
Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
123 citing papers in PubMed, 3 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- Systematic review and meta-analysis determining the benefits of in vivo genetic therapy in spinal muscular atrophy rodent models.Gene therapy · 2022Pooled it
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Exon skipping peptide-conjugated morpholinos downregulate dynamin 2 to rescue centronuclear myopathy.Brain : a journal of neurology · 2025Article
- Munc13-1 restoration mitigates presynaptic pathology in spinal muscular atrophy.Nature communications · 2025Article
- Widespread tissue delivery of antagomiRs via intramuscular administration.Molecular therapy. Methods & clinical development · 2025Article
- Whole-transcriptome sequencing in neural and non-neural tissues of a mouse model identifies miR-34a as a key regulator in SMA pathogenesis.Molecular therapy. Nucleic acids · 2025Article
- Article
- Review
- The Assembly of Fluorescently Labeled Peptide-Oligonucleotide Conjugates.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Morpholino-Mediated Exon Inclusion for Spinal Muscular Atrophy (SMA).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Use of Glucose/Fructose to Enhance the Exon Skipping Efficacy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Systemic Injection of Antisense Oligos into Spinal Muscular Atrophy (SMA) Mice and Evaluation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- In Vitro Evaluation of Antisense-Mediated Exon Inclusion for Spinal Muscular Atrophy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2025Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.