ArticleMolecular therapy. Nucleic acids2012
Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment.
Article in Molecular therapy. Nucleic acids, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
129 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.
- Muscle and cardiac therapeutic strategies for Duchenne muscular dystrophy: past, present, and future.Pharmacological reports : PR · 2020Pooled it
- Timing matters: Exon skipping therapy is most effective when initiated early in a mouse model of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2026Article
- Antisense oligonucleotide selection scheme for rare Duchenne muscular dystrophy mutations: Application toMolecular therapy. Nucleic acids · 2026Article
- Peptide-phosphorodiamidate morpholino oligomer therapy for dysferlinopathy induces pseudoexon skipping and restoration of functional protein.JCI insight · 2026Article
- CPP2Vec: A representation learning approach for cell-penetrating peptides prediction.PLoS computational biology · 2026Article
- PPMO-based exon skipping therapy improves respiratory function in theMolecular therapy. Nucleic acids · 2026Article
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- From molecular correction to functional rescue: delivery, tissue state, and immunobiology as the principal constraints on dystrophin-restoring therapy in Duchenne muscular dystrophy.Frontiers in pharmacology · 2026Review
- Transcytotic transportation of size-controlled nanocarriers into dystrophic skeletal muscle leads to therapeutic outcome in mice.Nature communications · 2025Article
- Genetic strategies for therapy of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2025Review
- Review
- Exon skipping peptide-conjugated morpholinos downregulate dynamin 2 to rescue centronuclear myopathy.Brain : a journal of neurology · 2025Article
- Progress and prospects in antisense oligonucleotide-mediated exon skipping therapies for Duchenne muscular dystrophy.Journal of muscle research and cell motility · 2025Review
- Aptamers as target-specific recognition elements in drug delivery.Advanced drug delivery reviews · 2025Review
- Molecular properties and intramolecular interactions of peptide-conjugated phosphorodiamidate morpholino oligonucleotides.Molecular therapy. Nucleic acids · 2025Article
- Optimisation of Heated Electrospray Ionisation Parameters to Minimise In-Source Generated Impurities in the Analysis of Oligonucleotide Therapeutics.Rapid communications in mass spectrometry : RCM · 2025Article
- DG9 boosts PMO nuclear uptake and exon skipping to restore dystrophic muscle and cardiac function.Nature communications · 2025Article
- Effect of chemical modification on the exon-skipping activity of heteroduplex oligonucleotides.Molecular therapy. Nucleic acids · 2025Article
- Nucleic Acid Conjugates: Unlocking Therapeutic Potential.ACS bio & med chem Au · 2025Review
- Targeting Drug Delivery System to Skeletal Muscles: A Comprehensive Review of Different Approaches.Journal of cachexia, sarcopenia and muscle · 2025Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.
Identifiers
What OpenQuestion holds
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.