ArticleThe Journal of clinical investigation2019
Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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
72 citing papers in PubMed.
- Peptide-phosphorodiamidate morpholino oligomer therapy for dysferlinopathy induces pseudoexon skipping and restoration of functional protein.JCI insight · 2026Article
- Pharmacokinetic/Pharmacodynamic Translation and Model-Informed Drug Development for Oligonucleotide Therapeutics.Journal of clinical pharmacology · 2026Review
- Impaired Myogenic Differentiation Is a Shared Feature Across Genetic Myopathies.International journal of molecular sciences · 2026Review
- Elimination of myotonia improves myopathy in a muscleblind-like knockout model of myotonic dystrophy.Nature communications · 2026Article
- Antibody-oligonucleotide conjugates: design principles, intracellular delivery, and translational opportunities.Journal of hematology & oncology · 2026Review
- Therapeutic Strategies Targeting the Molecular Pathogenesis of Myotonic Dystrophy Type 1: Current Status and Future Directions.Molecular diagnosis & therapy · 2026Review
- Bottlebrush polymer conjugates for enhanced antisense oligonucleotide therapy in myotonic dystrophy type 1.Nucleic acids research · 2026Article
- Sequence-Defined Digital Bottlebrush Polymers for Programmable Oligonucleotide Delivery.bioRxiv : the preprint server for biology · 2026Article
- CELF family of RNA-binding proteins: roles in disease biology and potential for therapeutic intervention.Cell communication and signaling : CCS · 2026Review
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Review
- Exon skipping peptide-conjugated morpholinos downregulate dynamin 2 to rescue centronuclear myopathy.Brain : a journal of neurology · 2025Article
- Cardiac Involvement in Myotonic Dystrophy Type 1: Mechanisms, Clinical Perspectives, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Elimination of myotonia improves myopathy in a muscleblind knockout model of myotonic dystrophy.bioRxiv : the preprint server for biology · 2025Article
- Repeat length as a key determinant for disease severity and antisense oligonucleotide activity in myotonic dystrophy type 1.Molecular therapy. Methods & clinical development · 2025Article
- Article
- Molecular genetics of myotonic dystrophy and the evolution of therapeutic approaches.Journal of human genetics · 2025Review
- Multisystem Symptoms in Myotonic Dystrophy Type 1: A Management and Therapeutic Perspective.International journal of molecular sciences · 2025Review
- Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
16 authors.
Funding
Abstract
Antisense oligonucleotides (ASOs) targeting pathologic RNAs have shown promising therapeutic corrections for many genetic diseases including myotonic dystrophy (DM1). Thus, ASO strategies for DM1 can abolish the toxic RNA gain-of-function mechanism caused by nucleus-retained mutant DMPK (DM1 protein kinase) transcripts containing CUG expansions (CUGexps). However, systemic use of ASOs for this muscular disease remains challenging due to poor drug distribution to skeletal muscle. To overcome this limitation, we test an arginine-rich Pip6a cell-penetrating peptide and show that Pip6a-conjugated morpholino phosphorodiamidate oligomer (PMO) dramatically enhanced ASO delivery into striated muscles of DM1 mice following systemic administration in comparison with unconjugated PMO and other ASO strategies. Thus, low-dose treatment with Pip6a-PMO-CAG targeting pathologic expansions is sufficient to reverse both splicing defects and myotonia in DM1 mice and normalizes the overall disease transcriptome. Moreover, treated DM1 patient-derived muscle cells showed that Pip6a-PMO-CAG specifically targets mutant CUGexp-DMPK transcripts to abrogate the detrimental sequestration of MBNL1 splicing factor by nuclear RNA foci and consequently MBNL1 functional loss, responsible for splicing defects and muscle dysfunction. Our results demonstrate that Pip6a-PMO-CAG induces long-lasting correction with high efficacy of DM1-associated phenotypes at both molecular and functional levels, and strongly support the use of advanced peptide conjugates for systemic corrective therapy in DM1.
Indexed as
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.