ArticleMolecular therapy. Nucleic acids2019
Scavenger Receptor Class A1 Mediates Uptake of Morpholino Antisense Oligonucleotide into Dystrophic Skeletal Muscle.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 27 citations in OpenAlex.
- DG9 boosts PMO nuclear uptake and exon skipping to restore dystrophic muscle and cardiac function.Nature communications · 2025Article
- Comparing Cell Penetration of Biotherapeutics across Human Cell Lines.ACS chemical biology · 2024Article
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- DG9-conjugated morpholino rescues phenotype in SMA mice by reaching the CNS via a subcutaneous administration.JCI insight · 2023Article
- Differential Uptake of Antisense Oligonucleotides in Mouse Hepatocytes and Macrophages Revealed by Simultaneous Two-Photon Excited Fluorescence and Coherent Raman Imaging.Nucleic acid therapeutics · 2022Article
- The nSMase2/Smpd3 gene modulates the severity of muscular dystrophy and the emotional stress response in mdx mice.BMC medicine · 2020Article
- Removal of the Polyglutamine Repeat of Ataxin-3 by Redirecting pre-mRNA Processing.International journal of molecular sciences · 2019Article
- In Vitro Validation of Phosphorodiamidate Morpholino Oligomers.Molecules (Basel, Switzerland) · 2019Article
- Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases.EBioMedicine · 2019Review
- Antisense-mediated splice intervention to treat human disease: the odyssey continues.F1000Research · 2019Review
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exon skipping using phosphorodiamidate morpholino oligomers (PMOs) is a promising treatment strategy for Duchenne muscular dystrophy (DMD). The most significant limitation of these clinically used compounds is their lack of delivery systems that target muscles; thus, cell-penetrating peptides are being developed to enhance uptake into muscles. Recently, we reported that uptake of peptide-conjugated PMOs into myofibers was mediated by scavenger receptor class A (SR-A), which binds negatively charged ligands. However, the mechanism by which the naked PMOs are taken up into fibers is poorly understood. In this study, we found that PMO uptake and exon-skipping efficiency were promoted in dystrophin-deficient myotubes via endocytosis through a caveolin-dependent pathway. Interestingly, SR-A1 was upregulated and localized in juxtaposition with caveolin-3 in these myotubes and promoted PMO-induced exon skipping. SR-A1 was also upregulated in the skeletal muscle of mdx52 mice and mediated PMO uptake. In addition, PMOs with neutral backbones had negative zeta potentials owing to their nucleobase compositions and interacted with SR-A1. In conclusion, PMOs with negative zeta potential were taken up into dystrophin-deficient skeletal muscle by upregulated SR-A1. Therefore, the development of a drug delivery system targeting SR-A1 could lead to highly efficient exon-skipping therapies for DMD.
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Registered trials
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