ArticleProceedings of the National Academy of Sciences of the United States of America2018
TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and vaccination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Cross-Neutralizing and Broadly Neutralizing Human Antibodies Against Nonenveloped Viruses.European journal of immunology · 2026Review
- Developing the next-generation of adenoviral vector vaccines.Human vaccines & immunotherapeutics · 2025Review
- State-selective small molecule degraders that preferentially remove aggregates and oligomers.Nature communications · 2025Article
- Orf virus-based vectors induce potent germinal center B cell, Tfh cell, and CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- mRNA prime-boost vaccination promotes clonal continuity in germinal center reactions and broadens SARS-CoV-2 variant coverage.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- AAV2.7m8 transduction of stage 2 human retinal organoids induces highly variable responses in innate and inflammatory gene expression and cytokine secretion.Experimental eye research · 2025Article
- Dendritic cell targeting in lymph nodes with modular adapters boosts HAdV5 and HC-HAdV5 tumor vaccination by co-secretion of IL-2v and IL-21.Molecular therapy. Oncology · 2025Article
- Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Understanding the performance of HIV-1 viral vector vaccines: adenovirus and poxvirus case studies.Frontiers in immunology · 2025Review
- Characterisation of post-translational and transcriptional reprogramming of the immune response to ISAV and IPNV infections in salmon head kidney cells.Frontiers in immunology · 2025Article
- Review
- Viral-mediated gene therapy in pediatric neurological disorders.World journal of pediatrics : WJP · 2024Review
- A causal multiomics study discriminates the early immune features of Ad5-vectored Ebola vaccine recipients.Innovation (Cambridge (Mass.)) · 2024Article
- Neoself Antigens Presented on MHC Class II Molecules in Autoimmune Diseases.Advances in experimental medicine and biology · 2024Article
- Innate Immune Response to Viral Vectors in Gene Therapy.Viruses · 2023Review
- Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models.Science (New York, N.Y.) · 2023Article
- Multiple Roles of TRIM21 in Virus Infection.International journal of molecular sciences · 2023Review
- Adenoviruses in medicine: innocuous pathogen, predator, or partner.Trends in molecular medicine · 2023Review
- Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer.Oncoimmunology · 2023Article
- Resistance towards ChadOx1 nCoV-19 in an 83 Years Old Woman Experiencing Vaccine Induced Thrombosis with Thrombocytopenia Syndrome.Vaccines · 2022Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Adenovirus has enormous potential as a gene-therapy vector, but preexisting immunity limits its widespread application. What is responsible for this immune block is unclear because antibodies potently inhibit transgene expression without impeding gene transfer into target cells. Here we show that antibody prevention of adenoviral gene delivery in vivo is mediated by the cytosolic antibody receptor TRIM21. Genetic KO of TRIM21 or a single-antibody point mutation is sufficient to restore transgene expression to near-naïve immune levels. TRIM21 is also responsible for blocking cytotoxic T cell induction by vaccine vectors, preventing a protective response against subsequent influenza infection and an engrafted tumor. Furthermore, adenoviral preexisting immunity can lead to an augmented immune response upon i.v. administration of the vector. Transcriptomic analysis of vector-transduced tissue reveals that TRIM21 is responsible for the specific up-regulation of hundreds of immune genes, the majority of which are components of the intrinsic or innate response. Together, these data define a major mechanism underlying the preimmune block to adenovirus gene therapy and demonstrate that TRIM21 efficiently blocks gene delivery in vivo while simultaneously inducing a rapid program of immune transcription.
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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.