ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Development of AAV-delivered broadly neutralizing anti-human ACE2 antibodies against SARS-CoV-2 variants.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- Long-term protective potency of AAV vector-based SARS-CoV-2 prophylaxis in mice and non-human primates.Frontiers in immunology · 2026Article
- Structural basis for childhood antibody recognition of the human metapneumovirus fusion protein.Nature communications · 2025Article
- Development of ACE2-tropic-betacoronavirus therapeutics for future pandemic preparedness.Nature communications · 2025Article
- Targeting ACE2 with a camelid antibody inhibits SARS-CoV-2 binding and has protective effects in vivo.Nature communications · 2025Article
- Structural Basis for Childhood Antibody Recognition of The Human Metapneumovirus Fusion Protein.bioRxiv : the preprint server for biology · 2025Article
- Teaching an old vector new tricks: the surprising versatility of AAV vaccines.Journal of virology · 2025Review
- Review
- AAV-based gene delivery of antimicrobial peptides to combat drug-resistant pathogens.Applied and environmental microbiology · 2025Review
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- MicroRNA-452-5p regulates fibrogenesis via targeting TGF-β/SMAD4 axis in SCN5A-knockdown human cardiac fibroblasts.iScience · 2024Article
- Application of the humanized mouse model in research into SARS-CoV-2 infection (Review).Medicine internationalReview
Corrections and comments
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Authors and funding
31 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.
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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.