ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Ex vivo and in vivo suppression of SARS-CoV-2 with combinatorial AAV/RNAi expression vectors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Distinct YY dinucleotide periodicity in adeno-associated virus DNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Comparative genomics identifies small interfering RNA with activity against all five human betacoronaviruses.Genome medicine · 2026Article
- Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness.Nature communications · 2025Article
- Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis.Nature genetics · 2025Article
- AAV-based gene delivery of antimicrobial peptides to combat drug-resistant pathogens.Applied and environmental microbiology · 2025Review
- High resistance barrier and prophylactic protection in preclinical models of SARS-CoV-2 with two siRNA combination.Nucleic acids research · 2025Article
- Evaluation of the effect of RNA secondary structure on Cas13d-mediated target RNA cleavage.Molecular therapy. Nucleic acids · 2024Article
- Complications of COVID-19 on the Central Nervous System: Mechanisms and Potential Treatment for Easing Long COVID.Aging and disease · 2023Review
- In vitro high-content tissue models to address precision medicine challenges.Molecular aspects of medicine · 2023Review
- Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Biochemistry-informed design selects potent siRNAs against SARS-CoV-2.RNA biology · 2023Article
- Can pulmonary RNA delivery improve our pandemic preparedness?Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Organoids and microphysiological systems: Promising models for accelerating AAV gene therapy studies.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite rapid development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant modalities to curb the pandemic by directly attacking the virus on a genetic level remain highly desirable and are urgently needed. Here we comprehensively illustrate the capacity of adeno-associated virus (AAV) vectors co-expressing a cocktail of three short hairpin RNAs (shRNAs; RNAi triggers) directed against the SARS-CoV-2 RdRp and N genes as versatile and effective antiviral agents. In cultured monkey cells and human gut organoids, our most potent vector, SAVIOR (SARS virus repressor), suppressed SARS-CoV-2 infection to background levels. Strikingly, in control experiments using single shRNAs, multiple SARS-CoV-2 escape mutants quickly emerged from infected cells within 24-48 h. Importantly, such adverse viral adaptation was fully prevented with the triple-shRNA AAV vector even during long-term cultivation. In addition, AAV-SAVIOR efficiently purged SARS-CoV-2 in a new model of chronically infected human intestinal cells. Finally, intranasal AAV-SAVIOR delivery using an AAV9 capsid moderately diminished viral loads and/or alleviated disease symptoms in hACE2-transgenic or wild-type mice infected with human or mouse SARS-CoV-2 strains, respectively. Our combinatorial and customizable AAV/RNAi vector complements ongoing global efforts to control the coronavirus disease 2019 (COVID-19) pandemic and holds great potential for clinical translation as an original and flexible preventive or therapeutic antiviral measure.
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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.