ArticleNucleic acids research2023
Targeted tissue delivery of RNA therapeutics using antibody-oligonucleotide conjugates (AOCs).
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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
77 citing papers in PubMed, 118 citations in OpenAlex.
- Article
- Ultrahigh-DAR antibody-drug conjugates: advancing the next generation of targeted therapy.Antibody therapeutics · 2026Article
- Antibody-drug conjugate engineering: from design to efficacy and safety.Signal transduction and targeted therapy · 2026Review
- 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
- An antisense method for efficient exon skipping and its application to Duchenne muscular dystrophy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- Targeting the non-coding RNA-PANoptosis axis: a novel frontier in disease diagnosis and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Antibody-oligonucleotide conjugates: design principles, intracellular delivery, and translational opportunities.Journal of hematology & oncology · 2026Review
- Delpacibart etedesiran improves the molecular pathology of myotonic dystrophy type 1 in the phase 1/2 MARINA study.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Therapeutic Strategies Targeting the Molecular Pathogenesis of Myotonic Dystrophy Type 1: Current Status and Future Directions.Molecular diagnosis & therapy · 2026Review
- Antibody-oligonucleotide conjugates: an emerging modality for precision RNA therapeutics.Antibody therapeutics · 2026Review
- Bottlebrush polymer conjugates for enhanced antisense oligonucleotide therapy in myotonic dystrophy type 1.Nucleic acids research · 2026Article
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Evaluation and forecasting of siRNA delivery technologies: An analysis of hierarchical decision model based on patent data.Molecular therapy. Nucleic acids · 2026Article
- RNA Therapeutics Targeting Skeletal Muscle: Emerging Antisense and Gene-Modifying Strategies.Biomolecules · 2026Review
- Research progress and development strategies of antibody-oligonucleotide conjugates.Gene therapy · 2026Review
- Therapeutic Spp1 silencing in TREM2Nature cardiovascular research · 2026Article
- Development of a Human IgG1 Monoclonal Antibody Targeting Transferrin Receptor 1 for Antitumor Drug Delivery.Antibodies (Basel, Switzerland) · 2026Article
- Development of a DUX4-targeting antibody oligonucleotide conjugate as a therapy for FSHD.Nucleic acids research · 2026Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although targeting TfR1 to deliver oligonucleotides to skeletal muscle has been demonstrated in rodents, effectiveness and pharmacokinetic/pharmacodynamic (PKPD) properties remained unknown in higher species. We developed antibody-oligonucleotide conjugates (AOCs) towards mice or monkeys utilizing anti-TfR1 monoclonal antibodies (αTfR1) conjugated to various classes of oligonucleotides (siRNA, ASOs and PMOs). αTfR1 AOCs delivered oligonucleotides to muscle tissue in both species. In mice, αTfR1 AOCs achieved a > 15-fold higher concentration to muscle tissue than unconjugated siRNA. A single dose of an αTfR1 conjugated to an siRNA against Ssb mRNA produced > 75% Ssb mRNA reduction in mice and monkeys, and mRNA silencing was greatest in skeletal and cardiac (striated) muscle with minimal to no activity in other major organs. In mice the EC50 for Ssb mRNA reduction in skeletal muscle was >75-fold less than in systemic tissues. Oligonucleotides conjugated to control antibodies or cholesterol produced no mRNA reduction or were 10-fold less potent, respectively. Tissue PKPD of AOCs demonstrated mRNA silencing activity primarily driven by receptor-mediated delivery in striated muscle for siRNA oligonucleotides. In mice, we show that AOC-mediated delivery is operable across various oligonucleotide modalities. AOC PKPD properties translated to higher species, providing promise for a new class of oligonucleotide therapeutics.
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.