ArticleProceedings of the National Academy of Sciences of the United States of America2023
Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The trial behind it
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Who cites it
34 citing papers in PubMed.
- Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.Research square · 2026Article
- Comparative genomics identifies small interfering RNA with activity against all five human betacoronaviruses.Genome medicine · 2026Article
- QStrain: an interactive platform for viral genome analysis and nucleic acid therapeutic design.BMC bioinformatics · 2026Article
- Intradermal delivery of lipophilic siRNAs enables prolonged skin retention and sustained gene silencing in a porcine model.Nature communications · 2026Article
- Respiratory Delivery of Highly Conserved Antiviral siRNAs Suppress SARS-CoV-2 Infection.International journal of molecular sciences · 2025Article
- DUSP11 is an Intracellular Innate Immune Checkpoint in Lung Adenocarcinoma.Cancer immunology research · 2025Article
- Delivery strategies for RNA-targeting therapeutic nucleic acids and RNA-based vaccines against respiratory RNA viruses: IAV, SARS-CoV-2, RSV.Molecular therapy. Nucleic acids · 2025Review
- RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Advances in locally administered nucleic acid therapeutics.Bioactive materials · 2025Review
- Systematic analysis of siRNA and mRNA features impacting fully chemically modified siRNA efficacy.Nucleic acids research · 2025Article
- Multimeric Conjugates Using Engineered Peptide Scaffolds for Efficient siRNA Delivery.Bioconjugate chemistry · 2025Article
- A Therapeutic Small-Interfering RNA Potentiates Janus Kinase 1 Modulation for the Treatment of Dog Inflammatory Diseases.ACS pharmacology & translational science · 2025Article
- Gene therapy then and now: A look back at changes in the field over the past 25 years.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver.Journal of medicinal chemistry · 2025Review
- High resistance barrier and prophylactic protection in preclinical models of SARS-CoV-2 with two siRNA combination.Nucleic acids research · 2025Article
- In Silico and In Vitro development of novel small interfering RNAs (siRNAs) to inhibit SARS-CoV-2.Computational and structural biotechnology journal · 2025Article
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Inhibition of SARS-CoV-2 growth in the lungs of mice by a peptide-conjugated morpholino oligomer targeting viral RNA.Molecular therapy. Nucleic acids · 2024Article
- Controversies and insights into PTBP1-related astrocyte-neuron transdifferentiation: neuronal regeneration strategies for Parkinson's and Alzheimer's disease.Translational neurodegeneration · 2024Review
- Anti-EGFR aptamer exhibits direct anti-cancer effects in NSCLC cells harboring EGFR L858R mutations.NPJ precision oncology · 2024Article
Corrections and comments
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Authors and funding
46 authors.
Funding
Abstract
The continuous evolution of SARS-CoV-2 variants complicates efforts to combat the ongoing pandemic, underscoring the need for a dynamic platform for the rapid development of pan-viral variant therapeutics. Oligonucleotide therapeutics are enhancing the treatment of numerous diseases with unprecedented potency, duration of effect, and safety. Through the systematic screening of hundreds of oligonucleotide sequences, we identified fully chemically stabilized siRNAs and ASOs that target regions of the SARS-CoV-2 genome conserved in all variants of concern, including delta and omicron. We successively evaluated candidates in cellular reporter assays, followed by viral inhibition in cell culture, with eventual testing of leads for in vivo antiviral activity in the lung. Previous attempts to deliver therapeutic oligonucleotides to the lung have met with only modest success. Here, we report the development of a platform for identifying and generating potent, chemically modified multimeric siRNAs bioavailable in the lung after local intranasal and intratracheal delivery. The optimized divalent siRNAs showed robust antiviral activity in human cells and mouse models of SARS-CoV-2 infection and represent a new paradigm for antiviral therapeutic development for current and future pandemics.
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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.