ArticleMolecular therapy. Nucleic acids2017
Inhibition of EGF Uptake by Nephrotoxic Antisense Drugs In Vitro and Implications for Preclinical Safety Profiling.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 33 citations in OpenAlex.
- Integrating transcriptomics and proteomics to assess antisense oligonucleotide safety and efficacy: a time-resolved approach.NAR molecular medicine · 2026Article
- Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1.American journal of human genetics · 2026Article
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Considerations in the Preclinical Assessment of the Safety of Antisense Oligonucleotides.Nucleic acid therapeutics · 2023Review
- Nephrotoxicity of marketed antisense oligonucleotide drugs.Current opinion in toxicology · 2022Article
- Silencing of ceramide synthase 2 in hepatocytes modulates plasma ceramide biomarkers predictive of cardiovascular death.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Antisense oligonucleotide is a promising intervention for liver diseases.Frontiers in pharmacology · 2022Review
- Antisense Oligonucleotide Technologies to Combat Obesity and Fatty Liver Disease.Frontiers in physiology · 2022Review
- Preclinical Safety Assessment of Therapeutic Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Preclinical Evaluation of the Renal Toxicity of Oligonucleotide Therapeutics in Mice.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Tissue heterogeneity is prevalent in gene expression studies.NAR genomics and bioinformatics · 2021Article
- Delivery of oligonucleotide-based therapeutics: challenges and opportunities.EMBO molecular medicine · 2021Review
- Antisense oligonucleotide development for the selective modulation of CYP3A5 in renal disease.Scientific reports · 2021Article
- Article
- GalNAc Conjugation Attenuates the Cytotoxicity of Antisense Oligonucleotide Drugs in Renal Tubular Cells.Molecular therapy. Nucleic acids · 2019Article
- Liver-Targeted Anti-HBV Single-Stranded Oligonucleotides with Locked Nucleic Acid Potently Reduce HBV Gene Expression In Vivo.Molecular therapy. Nucleic acids · 2018Article
- A Sensitive In Vitro Approach to Assess the Hybridization-Dependent Toxic Potential of High Affinity Gapmer Oligonucleotides.Molecular therapy. Nucleic acids · 2018Article
- Managing the sequence-specificity of antisense oligonucleotides in drug discovery.Nucleic acids research · 2017Review
- MicroRNAs and toxicology: A love marriage.Toxicology reports · 2017Review
- Assessing single-stranded oligonucleotide drug-induced effects in vitro reveals key risk factors for thrombocytopenia.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antisense oligonucleotide (AON) therapeutics offer new avenues to pursue clinically relevant targets inaccessible with other technologies. Advances in improving AON affinity and stability by incorporation of high affinity nucleotides, such as locked nucleic acids (LNA), have sometimes been stifled by safety liabilities related to their accumulation in the kidney tubule. In an attempt to predict and understand the mechanisms of LNA-AON-induced renal tubular toxicity, we established human cell models that recapitulate in vivo behavior of pre-clinically and clinically unfavorable LNA-AON drug candidates. We identified elevation of extracellular epidermal growth factor (EGF) as a robust and sensitive in vitro biomarker of LNA-AON-induced cytotoxicity in human kidney tubule epithelial cells. We report the time-dependent negative regulation of EGF uptake and EGF receptor (EGFR) signaling by toxic but not innocuous LNA-AONs and revealed the importance of EGFR signaling in LNA-AON-mediated decrease in cellular activity. The robust EGF-based in vitro safety profiling of LNA-AON drug candidates presented here, together with a better understanding of the underlying molecular mechanisms, constitutes a significant step toward developing safer antisense therapeutics.
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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.