ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Integrated Safety Assessment of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Considerations and recommendations for assessment of plasma protein binding and drug-drug interactions for siRNA therapeutics.Nucleic acids research · 2022Pooled it
- The Effects of 2'-O-Methoxyethyl Oligonucleotides on Renal Function in Humans.Nucleic acid therapeutics · 2018Pooled it
- Integrated Assessment of Phase 2 Data on GalNAcNucleic acid therapeutics · 2023Trial
- A Randomized, Double-Blind, Placebo-Controlled, First-Time-in-Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of GSK3389404 in Healthy Subjects.Clinical pharmacology in drug development · 2019Trial
- Integrated Assessment of the Clinical Performance of GalNAcNucleic acid therapeutics · 2019Trial
- Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis.The New England journal of medicine · 2018Trial
- Safety, tolerability, and pharmacokinetics of radavirsen (AVI-7100), an antisense oligonucleotide targeting influenza a M1/M2 translation.British journal of clinical pharmacology · 2018Trial
- Lack of QT Prolongation for 2'-O-Methoxyethyl-Modified Antisense Oligonucleotides Based on Retrospective Exposure/Response Analysis of Ten Phase 1 Dose-Escalation Placebo-Controlled Studies in Healthy Subjects.Nucleic acid therapeutics · 2017Trial
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- Expanding the toolbox: Emerging antisense oligonucleotide mechanisms for modulating gene expression.Molecular therapy. Nucleic acids · 2026Review
- Safety evaluation of an effervescent curcuminoids-ascorbic acid-polysaccharide-β-cyclodextrin (CUR-A-Poly-β-CD) inclusion complex powder in healthy volunteers: A non-placebo-controlled pilot study.Toxicology reports · 2026Article
- Addressing the needs of nano-rare patients: the n-Lorem experience.Nucleic acids research · 2026Review
- Model selection in preclinical nucleic acid therapeutics research.Communications biology · 2026Review
- Targeting Non-coding RNAs in Neurodegeneration: Advances in Therapeutic RNA Modalities and Next-Gen Delivery Technologies.Current Alzheimer research · 2026Review
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Review
- Gene expression silencing therapy in tumors, focus on gastrointestinal and genitourinary tumors.Frontiers in immunology · 2025Review
- Small RNA or oligonucleotide drugs and challenges in evaluating drug-drug interactions.Frontiers in pharmacology · 2025Review
- Synthetic-polymer-assisted antisense oligonucleotide delivery: targeted approaches for precision disease treatment.Beilstein journal of nanotechnology · 2025Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The common chemical and biological properties of antisense oligonucleotides provide the opportunity to identify and characterize chemical class effects across species. The chemical class that has proven to be the most versatile and best characterized is the 2'-O-methoxyethyl chimeric antisense oligonucleotides. In this report we present an integrated safety assessment of data obtained from controlled dose-ranging studies in nonhuman primates (macaques) and healthy human volunteers for 12 unique 2'-O-methoxyethyl chimeric antisense oligonucleotides. Safety was assessed by the incidence of safety signals in standardized laboratory tests for kidney and liver function, hematology, and complement activation; as well as by the mean test results as a function of dose level over time. At high doses a number of toxicities were observed in nonhuman primates. However, no class safety effects were identified in healthy human volunteers from this integrated data analysis. Effects on complement in nonhuman primates were not observed in humans. Nonhuman primates predicted safe doses in humans, but over predicted risk of complement activation and effects on platelets. Although limited to a single chemical class, comparisons from this analysis are considered valid and accurate based on the carefully controlled setting for the specified study populations and within the total exposures studied.
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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.