Trial reportMolecular therapy : the journal of the American Society of Gene Therapy2017
Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate.
Trial report in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 2 of them syntheses that pooled it.
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
106 citing papers in PubMed, 2 syntheses or guidelines pooled it, 203 citations in OpenAlex.
- Development of siRNA therapeutics to combat microbial infections: a bibliometric analysis.Frontiers in cellular and infection microbiology · 2025Pooled it
- Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins.Theranostics · 2021Pooled it
- Pharmacokinetic and Pharmacodynamic Properties of Cemdisiran, an RNAi Therapeutic Targeting Complement Component 5, in Healthy Subjects and Patients with Paroxysmal Nocturnal Hemoglobinuria.Clinical pharmacokinetics · 2021Trial
- Ligand conjugated antisense oligonucleotide for the treatment of transthyretin amyloidosis: preclinical and phase 1 data.ESC heart failure · 2021Trial
- Extracellular Vesicles in Cardiovascular Disease: Intercellular Signaling, Liquid Biopsy Biomarkers, and Therapeutic Translation.Circulation research · 2026Review
- Zilebesiran, a Small Interfering RNA Therapeutic Targeting Angiotensinogen: Mechanism, Clinical Evidence, Safety, and Implementation Considerations.Life (Basel, Switzerland) · 2026Review
- Recent Advances in Conjugation Chemistry Expanding the Applications of the DNA Tetrahedron.Chemical biology & drug design · 2026Review
- Evolution of siRNA Therapeutics: From Mechanistic Foundations to Clinical Expansion.Pharmaceutics · 2026Review
- Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.Nucleic acids research · 2026Article
- GalNAc-conjugated siRNA targeting C/EBPβ reverses metabolic dysfunction and restores liver homeostasis in a murine MASLD model.Molecular therapy. Nucleic acids · 2026Article
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Targeted Delivery of Nucleic Acid Therapeutics: Emerging Carriers and Applications in Common Metabolic and Inflammatory Diseases.International journal of nanomedicine · 2026Review
- Molecularly Built Ligands Degrade Membrane Receptors via Enhancing Their Accumulation in Lysosomes.ACS central science · 2025Article
- Optimization of siRNA therapeutics targeting MIAT for cardioprotection in myocardial ischemia/reperfusion injury.Molecular therapy. Nucleic acids · 2025Article
- Targeted therapeutic strategies as alternative and sustainable treatment options for obesity-induced steatohepatitis.Reviews in endocrine & metabolic disorders · 2025Review
- The Immune Microenvironment in Liver Cancer: From Analysis to Targeting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Targeting tumor immune evasion: the role of PD-L1 siRNA in advancing cancer immunotherapy.Medical oncology (Northwood, London, England) · 2025Review
- Development of a Modular Ribonucleoprotein Complex as a General Strategy to Deliver RNAi Therapeutics.Advanced healthcare materials · 2025Article
- Lepodisiran: From genetic targeting to cardiovascular promise: A detailed narrative review of the literature.World journal of cardiology · 2025Review
- Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advancement of RNAi-based therapeutics depends on effective delivery to the site of protein synthesis. Although intravenously administered, multi-component delivery vehicles have enabled small interfering RNA (siRNA) delivery and progression into clinical development, advances of single-component, systemic siRNA delivery have been challenging. In pre-clinical models, attachment of a triantennary N-acetylgalactosamine (GalNAc) ligand to an siRNA mediates hepatocyte uptake via the asialoglycoprotein receptor enabling RNAi-mediated gene silencing. In this phase 1 study, we assessed translation of this delivery approach by evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of a GalNAc-siRNA conjugate, revusiran, targeting transthyretin (TTR). Subjects received a placebo or ascending doses of revusiran subcutaneously ranging from 1.25-10 mg/kg in the single and 2.5-10 mg/kg in the multiple ascending dose phases. Revusiran was generally well tolerated, with transient, mild to moderate injection site reactions the most common treatment-emergent adverse events. Doses of 2.5-10 mg/kg revusiran elicited a significant reduction of serum TTR versus the placebo (p < 0.01), with mean TTR reductions of approximately 90% observed with multiple dosing. These results demonstrate translation of this novel delivery platform, enabling clinical development of subcutaneously administered GalNAc-siRNAs for liver-based diseases.
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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.