ReviewToxicologic pathology2018
The Nonclinical Safety Profile of GalNAc-conjugated RNAi Therapeutics in Subacute Studies.
Review in Toxicologic pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis 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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Safety profile of small interfering RNA therapeutics: a systematic review and meta-analysis of randomized controlled trials.Frontiers in drug safety and regulation · 2026Pooled it
- Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection.Antimicrobial agents and chemotherapy · 2025Trial
- Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules.Clinical pharmacokinetics · 2026Article
- Silencing of lncRNA HOTAIR Using Eyedrops as a Potential Treatment for Diabetes-Associated Retinal Dysregulation and Dysfunction.Investigative ophthalmology & visual science · 2026Article
- Design and systematic evaluation of novel chemical modification patterns enable the identification of a potent siRNA targetingMolecular therapy. Methods & clinical development · 2025Article
- Realizing the therapeutic potential of rapid knockdown of transthyretin via RNA interference in transthyretin amyloidosis.Molecular therapy. Nucleic acids · 2025Review
- Article
- Dual-targeted siRubicon delivery strategy triggers hepatocellular lipophagy for mitigating liver steatosis.Nature communications · 2025Article
- Characterization of Hepatotropic Small Molecule Inhibitors of Hypoxia Inducible Factor Prolyl Hydroxylase in the Prevention of Oxygen-Induced Retinopathy.Journal of medicinal chemistry · 2025Article
- Inhibition of Factor XI Using RBD4059: A Novel GalNAc-siRNA With Potent and Durable Antithrombotic Effects.JACC. Basic to translational science · 2025Article
- International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of Nonrodent Ocular Tissues.Toxicologic pathology · 2024Review
- Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- RNA interference in the era of nucleic acid therapeutics.Nature biotechnology · 2024Review
- Targeting the Liver with Nucleic Acid Therapeutics for the Treatment of Systemic Diseases of Liver Origin.Pharmacological reviews · 2023Review
- OSWG Recommended Approaches to the Nonclinical Pharmacokinetic (ADME) Characterization of Therapeutic Oligonucleotides.Nucleic acid therapeutics · 2023Article
- The N-Acetylgalactosamine-conjugated small interfering RNA inclisiran can be coadministered safely with atorvastatin in cynomolgus monkeys resulting in additive low-density lipoprotein cholesterol reductions.Pharmacology research & perspectives · 2023Article
- European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development.Toxicologic pathology · 2023Review
- Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Blood pressure-independent renoprotective effects of small interference RNA targeting liver angiotensinogen in experimental diabetes.British journal of pharmacology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Short interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) are the most clinically advanced oligonucleotide-based platforms. A number of N-acetylgalactosamine (GalNAc)-conjugated siRNAs (GalNAc-siRNAs), also referred to as RNA interference (RNAi) therapeutics, are currently in various stages of development, though none is yet approved. While the safety of ASOs has been the subject of extensive review, the nonclinical safety profiles of GalNAc-siRNAs have not been reported. With the exception of sequence differences that confer target RNA specificity, GalNAc-siRNAs are largely chemically uniform, containing limited number of phosphorothioate linkages, and 2'-O-methyl and 2'-deoxy-2'-fluoro ribose modifications. Here, we present the outcomes of short-term (3-5 week) rat and monkey weekly repeat-dose toxicology studies of six Enhanced Stabilization Chemistry GalNAc-siRNAs currently in clinical development. In nonclinical studies at supratherapeutic doses, these molecules share similar safety signals, with histologic findings in the organ of pharmacodynamic effect (liver), the organ of elimination (kidney), and the reticuloendothelial system (lymph nodes). The majority of these changes are nonadverse, partially to completely reversible, correlate well with pharmacokinetic parameters and tissue distribution, and often reflect drug accumulation. Furthermore, all GalNAc-siRNAs tested to date have been negative in genotoxicity and safety pharmacology studies.
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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.