ReviewNature biotechnology2017
The chemical evolution of oligonucleotide therapies of clinical utility.
Review in Nature biotechnology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 587 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
587 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,150 citations in OpenAlex.
- Safety profile of small interfering RNA therapeutics: a systematic review and meta-analysis of randomized controlled trials.Frontiers in drug safety and regulation · 2026Pooled it
- Antisense Versus Antigene in the Computer-Aided Design of Triplex-Forming Oligonucleotides (TFO): Insights from a Dual-Method Review, Combining Bibliometric and Systematic Review.International journal of molecular sciences · 2025Pooled it
- Exploring the Potential of PhosphoramideACS omega · 2026Article
- A versatile strategy for oligonucleotide functionalization via on-support phosphitylation.Nature chemistry · 2026Article
- Therapeutic upregulation of gene expression in inherited cardiomyopathies from current approaches to future directions.Nature cardiovascular research · 2026Review
- A 4'-Thioribouridine Modification Mimics 2'-O-Methoxyethyl in ASO-Like 20-Mers Targeting PTEN Knockdown.Chembiochem : a European journal of chemical biology · 2026Article
- Silencing with precision: In silico strategies for antisense oligonucleotide engineering.Molecular biology reports · 2026Review
- Review
- Safety and toxicity assessment of antisense oligonucleotides in brain-relevant human cellular models.Molecular therapy. Nucleic acids · 2026Review
- Accurately modeling RNase H-mediated antisense oligonucleotide efficacy.Molecular therapy. Nucleic acids · 2026Article
- A fully integrated sample-to-answer diagnostic platform enables rapid quantification of post-transplant infection at the point-of-care.Nature communications · 2026Article
- Sequence specificity of peptide nucleic acids containing terminal cationic amino acids.Bioorganic & medicinal chemistry · 2026Article
- RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine.International journal of molecular sciences · 2026Review
- Do Chemically Modified Oligonucleotide Therapeutics Require Environmental Risk Assessment?Environmental science & technology · 2026Article
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- Decreased Expression by a Chemically Modified siRNA to PTBP1 Seriously Affects Warburg Effect in Colorectal Cancer Cells.Cancer science · 2026Article
- Pharmacokinetic/Pharmacodynamic Translation and Model-Informed Drug Development for Oligonucleotide Therapeutics.Journal of clinical pharmacology · 2026Review
- Lipoprotein(a) in Coronary Artery Disease and Aortic Stenosis: Pathophysiology, Clinical Impact, Interventional Implications and Emerging Targeted Therapies.Journal of clinical medicine · 2026Review
- Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality in an MECP2 duplication mouse model.Nature communications · 2026Article
- Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?International journal of molecular sciences · 2026Review
527 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base sequence. Thus, as oligonucleotides with a particular chemical design show appropriate distribution and safety profiles for clinical gene silencing in a particular tissue, this will open the door to the rapid development of additional drugs targeting other disease-associated genes in the same tissue. To achieve clinical productivity, the chemical architecture of the oligonucleotide needs to be optimized with a combination of sugar, backbone, nucleobase, and 3'- and 5'-terminal modifications. A portfolio of chemistries can be used to confer drug-like properties onto the oligonucleotide as a whole, with minor chemical changes often translating into major improvements in clinical efficacy. One outstanding challenge in oligonucleotide chemical development is the optimization of chemical architectures to ensure long-term safety. There are multiple designs that enable effective targeting of the liver, but a second challenge is to develop architectures that enable robust clinical efficacy in additional tissues.
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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.