ArticleNucleic acids research2012
Target mRNA inhibition by oligonucleotide drugs in man.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
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- Delivery of oligonucleotides to bone marrow to modulate ferrochelatase splicing in a mouse model of erythropoietic protoporphyria.Nucleic acids research · 2020Article
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- Development of MTL-CEBPA: Small Activating RNA Drug for Hepatocellular Carcinoma.Current pharmaceutical biotechnology · 2018Review
- Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis.Molecules (Basel, Switzerland) · 2015Review
- Targeting microRNAs for immunomodulation.Current opinion in pharmacology · 2015Review
- Stereochemical bias introduced during RNA synthesis modulates the activity of phosphorothioate siRNAs.Nature communications · 2015Article
- Enzymatic synthesis of modified oligonucleotides by PEAR using Phusion and KOD DNA polymerases.Nucleic acid therapeutics · 2015Article
- Alicaforsen: An Emerging Therapeutic Agent for Ulcerative Colitis and Refractory Pouchitis.Gastroenterology research · 2014Review
- A chemical view of oligonucleotides for exon skipping and related drug applications.Nucleic acid therapeutics · 2014Review
- A phase 1 study of the BCL2-targeted deoxyribonucleic acid inhibitor (DNAi) PNT2258 in patients with advanced solid tumors.Cancer chemotherapy and pharmacology · 2014Article
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- RNA-guided diagnostics and therapeutics for next-generation individualized nanomedicine.The Journal of clinical investigation · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oligonucleotide delivery in vivo is commonly seen as the principal hurdle to the successful development of oligonucleotide drugs. In an analysis of 26 oligonucleotide drugs recently evaluated in late-stage clinical trials we found that to date at least half have demonstrated suppression of the target mRNA and/or protein levels in the relevant cell types in man, including those present in liver, muscle, bone marrow, lung, blood and solid tumors. Overall, this strongly implies that the drugs are being delivered to the appropriate disease tissues. Strikingly we also found that the majority of the drug targets of the oligonucleotides lie outside of the drugable genome and represent new mechanisms of action not previously investigated in a clinical setting. Despite the high risk of failure of novel mechanisms of action in the clinic, a subset of the targets has been validated by the drugs. While not wishing to downplay the technical challenges of oligonucleotide delivery in vivo, here we demonstrate that target selection and validation are of equal importance for the success of this field.
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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.