ArticleNucleic acids research2020
Mechanisms of palmitic acid-conjugated antisense oligonucleotide distribution in mice.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Barcoded oligonucleotide system (BOLT) for targeted organ delivery.Bioactive materials · 2027Article
- An RNA thermogenic therapy to preserve lean mass and enhance metabolic health during GLP-1 weight loss.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Antisense oligonucleotide selection scheme for rare Duchenne muscular dystrophy mutations: Application toMolecular therapy. Nucleic acids · 2026Article
- Fatty-acid-based antimiR-23b delivery in the DMSXL model: A potential therapeutic strategy for brain dysfunction in myotonic dystrophy type 1.Cell reports. Medicine · 2026Article
- Therapeutic Strategies Targeting the Molecular Pathogenesis of Myotonic Dystrophy Type 1: Current Status and Future Directions.Molecular diagnosis & therapy · 2026Review
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting.ACS applied materials & interfaces · 2026Article
- Strategies to Improve the Lipophilicity of Hydrophilic Macromolecular Drugs.Advanced healthcare materials · 2026Review
- Heteroduplex oligonucleotide technology boosts gene knockdown in cardiac and skeletal muscles.Nucleic acids research · 2026Article
- Endocytotic Albumin Uptake Pathways in Human Adipose Stem Cells and Connection to Intracellular Calcium Oscillations and the Neonatal Fc receptor.Cells, tissues, organs · 2026Article
- Systemic distribution of tricyclo-DNA antisense oligonucleotide following intratracheal instillation in the mouse.NAR molecular medicine · 2026Article
- C16-siRNAs in Focus: Development of ALN-APP, a Promising RNAi-Based Therapeutic for Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Potent and durable gene modulation in heart and muscle with chemically defined lipophilic siRNAs.Nucleic acids research · 2025Article
- Antisense oligonucleotide inhibition of HMGB1 attenuates angiotensin II-induced abdominal aortic aneurysms.Atherosclerosis · 2025Article
- Article
- Amphiphilic Oligonucleotide Derivatives-Promising Tools for Therapeutics.Pharmaceutics · 2024Review
- Heteroduplex oligonucleotide technology boosts oligonucleotide splice switching activity of morpholino oligomers in a Duchenne muscular dystrophy mouse model.Nature communications · 2024Article
- RNAi mediated silencing of STAT3/PD-L1 in tumor-associated immune cells induces robust anti-tumor effects in immunotherapy resistant tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Characterizing the plasma protein binding profiles of chemistry diversified antisense oligonucleotides in human and mouse plasma using an ultrafiltration method.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conjugation of antisense oligonucleotide (ASO) with a variety of distinct lipophilic moieties like fatty acids and cholesterol increases ASO accumulation and activity in multiple tissues. While lipid conjugation increases tissue exposure in mice and reduces excretion of ASO in urine, histological review of skeletal and cardiac muscle indicates that the increased tissue accumulation of lipid conjugated ASO is isolated to the interstitium. Administration of palmitic acid-conjugated ASO (Palm-ASO) in mice results in a rapid and substantial accumulation in the interstitium of muscle tissue followed by relatively rapid clearance and only slight increases in intracellular accumulation in myocytes. We propose a model whereby increased affinity for lipid particles, albumin, and other plasma proteins by lipid-conjugation facilitates ASO transport across endothelial barriers into tissue interstitium. However, this increased affinity for lipid particles and plasma proteins also facilitates the transport of ASO from the interstitium to the lymph and back into circulation. The cumulative effect is only a slight (∼2-fold) increase in tissue accumulation and similar increase in ASO activity. To support this proposal, we demonstrate that the activity of lipid conjugated ASO was reduced in two mouse models with defects in endothelial transport of macromolecules: caveolin-1 knockout (Cav1-/-) and FcRn knockout (FcRn-/-).
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