ArticleNucleic acids research2017
Asialoglycoprotein receptor 1 mediates productive uptake of N-acetylgalactosamine-conjugated and unconjugated phosphorothioate antisense oligonucleotides into liver hepatocytes.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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The trial behind it
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Who cites it
91 citing papers in PubMed, 155 citations in OpenAlex.
- Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy.Circulation. Heart failure · 2026Trial
- Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection.Antimicrobial agents and chemotherapy · 2025Trial
- A single ascending dose study of single-stranded oligodeoxyribonucleotide RO7062931 in Chinese healthy volunteers.Clinical and translational science · 2023Trial
- Clinical Study of Single-Stranded Oligonucleotide RO7062931 in Healthy Volunteers and Patients With Chronic Hepatitis B.Hepatology (Baltimore, Md.) · 2021Trial
- Ligand conjugated antisense oligonucleotide for the treatment of transthyretin amyloidosis: preclinical and phase 1 data.ESC heart failure · 2021Trial
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery.The Journal of cell biology · 2026Article
- The asialoglycoprotein receptor 1 (ASGR1): emerging new roles in health and disease.Biomarker research · 2026Review
- A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs.Clinical and translational science · 2026Article
- Extracellular and Membrane Protein: Structure, Biological Functions, Diseases, and an Emerging Modality for Drug Discovery.MedComm · 2026Review
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Antisense oligonucleotides: targeting oncogenic long non-coding RNAs for cancer therapy.Biotechnology letters · 2026Review
- Targeted Protein Degradation in Cancer: PROTACs, New Targets, and Clinical Mechanisms.Biomolecules · 2026Review
- [Anti-inflammatory effects of cell membrane vesicle-mediated delivery of small interfering RNA targeting tumor necrosis factor-α on dental pulp stem cells].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Article
- Donidalorsen for the Treatment of Hereditary Angioedema: A Review of Clinical Studies.Drug design, development and therapy · 2026Review
- An unbiased whole-genome open reading frame overexpression screen identifies B3GALT2, a novel inducer of cellular ASO activity.Molecular therapy. Nucleic acids · 2025Article
- Pharmaceutical perspectives on oligonucleotide therapeutics and delivery systems.Pharmacological reviews · 2025Review
- The Progress and Evolving Trends in Nucleic-Acid-Based Therapies.Biomolecules · 2025Review
- Article
- Lipid Nanovesicles in Cancer Treatment: Improving Targeting and Stability of Antisense Oligonucleotides.Drug design, development and therapy · 2025Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antisense oligonucleotide (ASO) therapeutics show tremendous promise for the treatment of previously intractable human diseases but to exert their effects on cellular RNA processing they must first cross the plasma membrane by endocytosis. The conjugation of ASOs to a receptor ligand can dramatically increase their entry into certain cells and tissues, as demonstrated by the implementation of N-acetylgalactosamine (GalNAc)-conjugated ASOs for Asialoglycoprotein Receptor (ASGR)-mediated uptake into liver hepatocytes. We compared the internalization and activity of GalNAc-conjugated ASOs and their parents in endogenous ASGR-expressing cells and were able to recapitulate hepatocyte ASO uptake and activity in cells engineered to heterologously express the receptor. We found that the minor receptor subunit, ASGR2, is not required for effective in vitro or in vivo uptake of GalNAc-conjugated ASO and that the major subunit, ASGR1, plays a small but significant role in the uptake of unconjugated phosphorothioate ASOs into hepatocytes. Moreover, our data demonstrates there is a large excess capacity of liver ASGR for the effective uptake of GalNAc-ASO conjugates, suggesting broad opportunities to exploit receptors with relatively moderate levels of expression.
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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.