ArticleJournal of controlled release : official journal of the Controlled Release Society2022
Inhibition of SARS-CoV-2 replication in the lung with siRNA/VIPER polyplexes.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Comparative genomics identifies small interfering RNA with activity against all five human betacoronaviruses.Genome medicine · 2026Article
- Therapeutic Bioactivity Exerted by theMolecules (Basel, Switzerland) · 2025Article
- Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV.Drug delivery and translational research · 2025Review
- Analysis of Polymer/siRNA Nanoparticle Efficacy and Biocompatibility in 3D Air-Liquid Interface Culture Compared to 2D Cell Culture.Pharmaceutics · 2025Article
- Potential Broad-Spectrum Antiviral Agents: A Key Arsenal Against Newly Emerging and Reemerging Respiratory RNA Viruses.International journal of molecular sciences · 2025Review
- Nanoparticle-Mediated siRNA Delivery in Human Epithelial Lung Cells Cultured at the Air-Liquid Interface.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Advances and Challenges in Antiviral Development for Respiratory Viruses.Pathogens (Basel, Switzerland) · 2024Review
- Evaluation of the effect of RNA secondary structure on Cas13d-mediated target RNA cleavage.Molecular therapy. Nucleic acids · 2024Article
- Pulmonary siRNA Delivery with Sophisticated Amphiphilic Poly(Spermine Acrylamides) for the Treatment of Lung Fibrosis.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Review
- Fluorescent Techniques for RNA Detection in Nanoparticles.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Optimization of Lung Surfactant Coating of siRNA Polyplexes for Pulmonary Delivery.Pharmaceutical research · 2024Article
- Targeted Molecular Therapeutics for Pulmonary Diseases: Addressing the Need for Precise Drug Delivery.Handbook of experimental pharmacology · 2024Article
- Intranasal Drug Delivery by Nanotechnology: Advances in and Challenges for Alzheimer's Disease Management.Pharmaceutics · 2023Review
- Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services.Journal of personalized medicine · 2023Article
- Nano-Enabled Antivirals for Overcoming Antibody Escaped Mutations Based SARS-CoV-2 Waves.International journal of molecular sciences · 2023Review
- Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections.Pharmaceutical research · 2023Review
- Article
- Functional nucleic acids as potent therapeutics against SARS-CoV-2 infection.Cell reports. Physical science · 2023Review
- Directing the Way-Receptor and Chemical Targeting Strategies for Nucleic Acid Delivery.Pharmaceutical research · 2023Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
SARS-CoV-2 has been the cause of a global pandemic since 2019 and remains a medical urgency. siRNA-based therapies are a promising strategy to fight viral infections. By targeting a specific region of the viral genome, siRNAs can efficiently downregulate viral replication and suppress viral infection. However, to achieve the desired therapeutic activity, siRNA requires a suitable delivery system. The VIPER (virus-inspired polymer for endosomal release) block copolymer has been reported as promising delivery system for both plasmid DNA and siRNA in the past years. It is composed of a hydrophilic block for condensation of nucleic acids as well as a hydrophobic, pH-sensitive block that, at acidic pH, exposes the membrane lytic peptide melittin, which enhances endosomal escape. In this study, we aimed at developing a formulation for pulmonary administration of siRNA to suppress SARS-CoV-2 replication in lung epithelial cells. After characterizing siRNA/VIPER polyplexes, the activity and safety profile were confirmed in a lung epithelial cell line. To further investigate the activity of the polyplexes in a more sophisticated cell culture system, an air-liquid interface (ALI) culture was established. siRNA/VIPER polyplexes reached the cell monolayer and penetrated through the mucus layer secreted by the cells. Additionally, the activity against wild-type SARS-CoV-2 in the ALI model was confirmed by qRT-PCR. To investigate translatability of our findings, the activity against SARS-CoV-2 was tested ex vivo in human lung explants. Here, siRNA/VIPER polyplexes efficiently inhibited SARS-CoV-2 replication. Finally, we verified the delivery of siRNA/VIPER polyplexes to lung epithelial cells in vivo, which represent the main cellular target of viral infection in the lung. In conclusion, siRNA/VIPER polyplexes efficiently delivered siRNA to lung epithelial cells and mediated robust downregulation of viral replication both in vitro and ex vivo without toxic or immunogenic side effects in vivo, demonstrating the potential of local siRNA delivery as a promising antiviral therapy in the lung.
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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.