ArticleNucleic acids research2025
Conjugation to a transferrin receptor 1-binding Bicycle peptide enhances ASO and siRNA potency in skeletal and cardiac muscles.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Article
- Neutral Backbone Modifications Enhance the Pharmacokinetics and Biodistribution of Antibody-Oligonucleotide Conjugates with High Drug-to-Antibody Ratios.Journal of medicinal chemistry · 2026Article
- A positively selected microRNA controls a reversible aging program in striated muscle.bioRxiv : the preprint server for biology · 2026Article
- Targeting the non-coding RNA-PANoptosis axis: a novel frontier in disease diagnosis and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Review
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Bottlebrush polymer conjugates for enhanced antisense oligonucleotide therapy in myotonic dystrophy type 1.Nucleic acids research · 2026Article
- RNA-Based Therapies for Treating Monogenic Cardiomyopathies.The Canadian journal of cardiology · 2026Review
- The 2025 Oligo Meeting in Budapest: Highlights of the 21Molecular therapy. Nucleic acids · 2026Article
- Transient acute neuronal activation response caused by high concentrations of oligonucleotides in the cerebral spinal fluid.Nucleic acids research · 2026Article
- Versatile introduction of multifunctional Michael-acceptor moieties on amino-oligonucleotides for bioconjugation purposes.Communications chemistry · 2026Article
- Potent and durable gene modulation in heart and muscle with chemically defined lipophilic siRNAs.Nucleic acids research · 2025Article
- A systemically deliverable lipid-conjugated siRNA targeting DUX4 as an facioscapulohumeral muscular dystrophy therapeutic.Molecular therapy. Methods & clinical development · 2025Article
Corrections and comments
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Authors and funding
30 authors.
Funding
Abstract
Improving the delivery of antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to skeletal and cardiac muscles remains a pivotal task toward the broader application of oligonucleotide therapeutics. The targeting of myofibers and cardiomyocytes via conjugation of ASOs and siRNAs to ligands that bind the human transferrin receptor 1 (TfR1) has gathered significant interest in recent years. However, the selection of ligands with low molecular weight and optimal biophysical and binding properties is crucial to maximize the potential of the TfR1 ligand-conjugated antisense (LICA) technology. Here, through effective combination of phage display and peptide medicinal chemistry, we identified and characterized a bicyclic peptide (Bicycle® molecule BCY17901), with a molecular weight of ∼2 kDa, that binds human TfR1 with high affinity and specificity. Conjugation to BCY17901 improved ASO and siRNA potency in skeletal and cardiac muscles of human TfR1 knock-in mice, after either intravenous or subcutaneous administration. Furthermore, single-nucleus RNA sequencing showed that conjugation to BCY17901 enhanced ASO activity in myonuclei of different muscle fiber types. Importantly, we demonstrated good translatability of our TfR1-targeting platform in skeletal and cardiac muscles of nonhuman primates. Our results offer great promise toward potential future applications of low-molecular-weight Bicycle LICA therapeutics for the treatment of diseases affecting skeletal muscle and heart.
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Registered trials
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