ArticleMolecular therapy. Nucleic acids2016
Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates.
Article in Molecular therapy. Nucleic acids, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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 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.
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 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
- Targeting lncRNAs to Overcome Cancer Therapy Resistance: Advances in RNA Therapeutics and Delivery Strategies.Cancers · 2026Review
- miRNA-lncRNA Cross-Regulation Landscape in Cancer: From Molecular Mechanisms to Therapeutic and Diagnostic Applications.Cancers · 2026Review
- RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review.Pharmaceutics · 2026Review
- LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation.Molecular therapy. Nucleic acids · 2024Article
- MiR-134-5p inhibits the malignant phenotypes of osteosarcoma via ITGB1/MMP2/PI3K/Akt pathway.Cell death discovery · 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
- miRNA-Based Technologies in Cancer Therapy.Journal of personalized medicine · 2023Review
- Localization of unlabeled bepirovirsen antisense oligonucleotide in murine tissues using in situ hybridization and CARS imaging.RNA (New York, N.Y.) · 2023Article
- 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
- Review
- Bioanalysis of Oligonucleotide by LC-MS: Effects of Ion Pairing Regents and Recent Advances in Ion-Pairing-Free Analytical Strategies.International journal of molecular sciences · 2022Review
- miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.Molecular therapy. Nucleic acids · 2022Review
- Antisense Oligonucleotide-Based Therapy on miR-181a-5p Alleviates Cartilage Degradation of Temporomandibular Joint OsteoarthritisFrontiers in pharmacology · 2022Article
- miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy.Cancers · 2021Review
- Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.Signal transduction and targeted therapy · 2021Review
- MicroRNAs in Basolateral Amygdala Associated with Stress and Fear Memories Regulate Rapid Eye Movement Sleep in Rats.Brain sciences · 2021Article
- Review
- microRNAs as Novel Therapeutics in Cancer.Cancers · 2021Review
- Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma.Cells · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis) plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i-miR-221 in plasma and urine, while a specific in situ hybridization assay for tissue uptake analysis was designed. Our analysis revealed short half-life, optimal tissue biovailability and minimal urine excretion of LNA-i-miR-221 in mice and monkeys. Up to 3 weeks, LNA-i-miR-221 was still detectable in mice vital organs and in xenografted tumors, together with p27 target upregulation. Importantly, no toxicity in the pilot monkey study was observed. Overall, our findings indicate the suitability of LNA-i-miR-221 for clinical use and we provide here pilot data for safety analysis and further development of LNA-miRNA-based therapeutics for human cancer.
Identifiers
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.