ArticleNature biotechnology2019
A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system.
Article in Nature biotechnology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
What it found
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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
149 citing papers in PubMed, 221 citations in OpenAlex.
- Barcoded oligonucleotide system (BOLT) for targeted organ delivery.Bioactive materials · 2027Article
- A versatile strategy for oligonucleotide functionalization via on-support phosphitylation.Nature chemistry · 2026Article
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.Nucleic acids research · 2026Article
- A Dual-Halogen Labeling Strategy to Detect and Quantify Double-Stranded RNAs Using NanoSIMS: A Proof-of-Concept Study.ACS omega · 2026Article
- Fatty-acid-based antimiR-23b delivery in the DMSXL model: A potential therapeutic strategy for brain dysfunction in myotonic dystrophy type 1.Cell reports. Medicine · 2026Article
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Pharmacokinetic/Pharmacodynamic Translation and Model-Informed Drug Development for Oligonucleotide Therapeutics.Journal of clinical pharmacology · 2026Review
- Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality in an MECP2 duplication mouse model.Nature communications · 2026Article
- Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.Research square · 2026Article
- Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease-Unveiling challenges and prospects.International journal of pharmaceutics: X · 2026Review
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.Genes · 2026Review
- An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.Molecular therapy. Nucleic acids · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- Gene therapy for huntington's disease: advances, challenges, and future perspectives.Neurogenetics · 2026Review
- Advancements in RNA-based therapies from bench to bedside.npj drug discovery · 2026Review
- Model selection in preclinical nucleic acid therapeutics research.Communications biology · 2026Review
- Intradermal delivery of lipophilic siRNAs enables prolonged skin retention and sustained gene silencing in a porcine model.Nature communications · 2026Article
- RNA-Micelles as Self-Assembling Structures for Efficient Co-Delivery of Synergistic siRNA and Nucleoside Analogues to Treat CRC Lung Metastasis.Advanced functional materials · 2026Article
- ZnJournal of nanobiotechnology · 2026Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 3 institutions in 1 country.
Funding
Abstract
Sustained silencing of gene expression throughout the brain using small interfering RNAs (siRNAs) has not been achieved. Here we describe an siRNA architecture, divalent siRNA (di-siRNA), that supports potent, sustained gene silencing in the central nervous system (CNS) of mice and nonhuman primates following a single injection into the cerebrospinal fluid. Di-siRNAs are composed of two fully chemically modified, phosphorothioate-containing siRNAs connected by a linker. In mice, di-siRNAs induced the potent silencing of huntingtin, the causative gene in Huntington's disease, reducing messenger RNA and protein throughout the brain. Silencing persisted for at least 6 months, with the degree of gene silencing correlating to levels of guide strand tissue accumulation. In cynomolgus macaques, a bolus injection of di-siRNA showed substantial distribution and robust silencing throughout the brain and spinal cord without detectable toxicity and with minimal off-target effects. This siRNA design may enable RNA interference-based gene silencing in the CNS for the treatment of neurological disorders.
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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.