ArticleMolecular therapy. Nucleic acids2020
Dose-Finding Study and Pharmacokinetics Profile of the Novel 13-Mer Antisense miR-221 Inhibitor in Sprague-Dawley Rats.
Article in Molecular therapy. Nucleic acids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04811898 (A Dose Escalation Phase I Study of LNA-i-miR-221 for the Treatment of Refractory Multiple Myeloma and Advanced Solid Tumors), which is not on this map. Cited by 12 papers, 1 of them a synthesis 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.
A Dose Escalation Phase I Study of LNA-i-miR-221 for the Treatment of Refractory Multiple Myeloma and Advanced Solid Tumors
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- A systematic review of non-coding RNA therapeutics in early clinical trials: a new perspective against cancer.Journal of translational medicine · 2024Pooled it
- Single-base 2'OMe-modified LNA and MOE gapmers selectively silenceMolecular therapy. Nucleic acids · 2026Article
- The Role of miRNAs in Retinal Physiology and in Inherited Retinal Disorders.Physiology (Bethesda, Md.) · 2026Review
- RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review.Pharmaceutics · 2026Review
- MicroRNA in cancer therapy: breakthroughs and challenges in early clinical applications.Journal of experimental & clinical cancer research : CR · 2025Review
- LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation.Molecular therapy. Nucleic acids · 2024Article
- Scaling approaches for the prediction of human clearance of LNA-i-mir-221: A retrospective validation.Current research in pharmacology and drug discovery · 2024Article
- Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study.Journal of hematology & oncology · 2023Article
- miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.Molecular therapy. Nucleic acids · 2022Review
- Roles of miRNA dysregulation in the pathogenesis of multiple myeloma.Cancer gene therapy · 2021Review
- Review
- In vivo uptake of antisense oligonucleotide drugs predicted by ab initio quantum mechanical calculations.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
miR-221 is overexpressed in several malignancies where it promotes tumor growth and survival by interfering with gene transcripts, including p27Kip1, PUMA, PTEN, and p57Kip2. We previously demonstrated that a novel 13-mer miR-221 inhibitor (locked nucleic acid [LNA]-i-miR-221) exerts antitumor activity against human cancer with a pilot-favorable pharmacokinetics and safety profile in mice and non-naive monkeys. In this study, we report a non-good laboratory practice (GLP)/GLP dose-finding investigation of LNA-i-miR-221 in Sprague-Dawley rats. The safety of the intravenous dose (125 mg/kg/day) for 4 consecutive days, two treatment cycles, was investigated by a first non-GLP study. The toxicokinetics profile of LNA-i-miR-221 was next explored in a GLP study at three different doses (5, 12.5, and 125 mg/kg/day). Slight changes in blood parameters and histological findings in kidney were observed at the highest dose. These effects were reversible and consistent with an in vivo antisense oligonucleotide (ASO) class effect. The no-observed-adverse-effect level (NOAEL) was established at 5 mg/kg/day. The plasma exposure of LNA-i-miR-221, based on C
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