ArticleNature biotechnology2014
Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications.
Article in Nature biotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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
76 citing papers in PubMed, 187 citations in OpenAlex.
- A versatile strategy for oligonucleotide functionalization via on-support phosphitylation.Nature chemistry · 2026Article
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- Knocking on Cells' Door: Strategic Approaches for miRNA and siRNA in Anticancer Therapy.International journal of molecular sciences · 2025Review
- Frosted DNA: β-Galactosidase Control of Oligonucleotide Activity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Synthesis, Biophysical and Biological Evaluation of Splice-Switching Oligonucleotides with Multiple LNA-Phosphothiotriester Backbones.Journal of the American Chemical Society · 2024Article
- Structure-Activity Relationship of Antibody-Oligonucleotide Conjugates: Evaluating Bioconjugation Strategies for Antibody-siRNA Conjugates for Drug Development.Journal of medicinal chemistry · 2024Article
- Article
- Synthesis and Properties of Oligonucleotides Containing LNA-Sulfamate and Sulfamide Backbone Linkages.Organic letters · 2024Article
- Triazole-linked Nucleic Acids: Synthesis, Therapeutics and Synthetic Biology Applications.Current organic synthesis · 2024Review
- Design, Synthesis, and Biochemical Analysis of a Molecule Designed to Enhance Endosomal Escape.The AAPS journal · 2023Article
- Synthesis of biolabile thioalkyl-protected phosphates from an easily accessible phosphotriester precursor.Chemical science · 2023Article
- A Triazolium-Anchored Self-Immolative Linker Enables Self-Assembly-Driven siRNA Binding and Esterase-Induced Release.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Structural Modifications of siRNA Improve Its Performance In Vivo.International journal of molecular sciences · 2023Review
- RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.The Journal of pharmacology and experimental therapeutics · 2023Review
- Transdermal delivery for gene therapy.Drug delivery and translational research · 2022Review
- Delivery of RNA Therapeutics: The Great Endosomal Escape!Nucleic acid therapeutics · 2022Review
- The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides.Pharmaceuticals (Basel, Switzerland) · 2022Review
- An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides.Nature communications · 2022Article
- Tetrazine-Induced Bioorthogonal Activation of Vitamin E-Modified siRNA for Gene Silencing.Molecules (Basel, Switzerland) · 2022Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
RNA interference (RNAi) has great potential to treat human disease. However, in vivo delivery of short interfering RNAs (siRNAs), which are negatively charged double-stranded RNA macromolecules, remains a major hurdle. Current siRNA delivery has begun to move away from large lipid and synthetic nanoparticles to more defined molecular conjugates. Here we address this issue by synthesis of short interfering ribonucleic neutrals (siRNNs) whose phosphate backbone contains neutral phosphotriester groups, allowing for delivery into cells. Once inside cells, siRNNs are converted by cytoplasmic thioesterases into native, charged phosphodiester-backbone siRNAs, which induce robust RNAi responses. siRNNs have favorable drug-like properties, including high synthetic yields, serum stability and absence of innate immune responses. Unlike siRNAs, siRNNs avidly bind serum albumin to positively influence pharmacokinetic properties. Systemic delivery of siRNNs conjugated to a hepatocyte-specific targeting domain induced extended dose-dependent in vivo RNAi responses in mice. We believe that siRNNs represent a technology that will open new avenues for development of RNAi therapeutics.
Indexed as
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.