ArticleNucleic acids research2016
Stabilin-1 and Stabilin-2 are specific receptors for the cellular internalization of phosphorothioate-modified antisense oligonucleotides (ASOs) in the liver.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 163 citations in OpenAlex.
- Article
- Neutral Backbone Modifications Enhance the Pharmacokinetics and Biodistribution of Antibody-Oligonucleotide Conjugates with High Drug-to-Antibody Ratios.Journal of medicinal chemistry · 2026Article
- EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery.The Journal of cell biology · 2026Article
- The Scavenger Function of LSECs, a Regulator of Liver Diseases.Current issues in molecular biology · 2026Review
- The endothelial scavenger receptorbioRxiv : the preprint server for biology · 2026Article
- Synthesis of highly complex phosphorothioate-modified oligonucleotides on microarrays.Scientific reports · 2026Article
- Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting.ACS applied materials & interfaces · 2026Article
- Antisense Oligonucleotides: Technological Advances, Clinical Progress, and Expanding Therapeutic Frontiers.Pharmaceutics · 2026Review
- Assessing Cell-Specific Delivery and Efficacy of Therapeutic Oligonucleotides Using Combined RNAscope Plus and Protein Multiplexing in FFPE Tissue.Methods in molecular biology (Clifton, N.J.) · 2026Article
- An unbiased whole-genome open reading frame overexpression screen identifies B3GALT2, a novel inducer of cellular ASO activity.Molecular therapy. Nucleic acids · 2025Article
- A genome-wide CRISPR screen unveils the endosomal maturation protein WDR91 as a promoter of productive ASO activity in melanoma.Molecular therapy. Nucleic acids · 2025Article
- Long non-coding RNAMolecular therapy. Nucleic acids · 2025Review
- 2'-O-methylation and N6-methyladenosine enhance the oral delivery of small RNAs in mice.Molecular therapy. Nucleic acids · 2025Article
- Exosomes as nanocarriers for brain-targeted delivery of therapeutic nucleic acids: advances and challenges.Journal of nanobiotechnology · 2025Review
- Clinical applications of oligonucleotides for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Chondroitin Sulfate-Coated Heteroduplex-Molecular Spherical Nucleic Acids.Chembiochem : a European journal of chemical biology · 2025Article
- Synthesis and Application of 4'-Molecules (Basel, Switzerland) · 2025Article
- Quantifying and mitigating motor phenotypes induced by antisense oligonucleotides in the central nervous system.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
- Multimodal imaging of a liver-on-a-chip model using labelled and label-free optical microscopy techniques.Lab on a chip · 2024Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphorothioate (PS)-modified antisense oligonucleotides (ASOs) have been extensively investigated over the past three decades as pharmacological and therapeutic agents. One second generation ASO, Kynamro™, was recently approved by the FDA for the treatment of homozygous familial hypercholesterolemia and over 35 second generation PS ASOs are at various stages of clinical development. In this report, we show that the Stabilin class of scavenger receptors, which were not previously thought to bind DNA, do bind and internalize PS ASOs. With the use of primary cells from mouse and rat livers and recombinant cell lines each expressing Stabilin-1 and each isoform of Stabilin-2 (315-HARE and 190-HARE), we have determined that PS ASOs bind with high affinity and these receptors are responsible for bulk, clathrin-mediated endocytosis within the cell. Binding is primarily dependent on salt-bridge formation and correct folding of the intact protein receptor. Increased internalization rates also enhanced ASO potency for reducing expression of the non-coding RNA Malat-1, in Stabilin-expressing cell lines. A more thorough understanding of mechanisms by which ASOs are internalized in cells and their intracellular trafficking pathways will aid in the design of next generation antisense agents with improved therapeutic properties.
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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.