ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Ad5:Ad48 hexon hypervariable region substitutions lead to toxicity and increased inflammatory responses following intravenous delivery.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
- First-in-human evaluation of a hexon chimeric adenovirus vector expressing HIV-1 Env (IPCAVD 002).The Journal of infectious diseases · 2014Trial
- Defining the safety and efficacy of liver-directed AAV gene therapy using a human liver tissue-equivalent platform.Molecular therapy. Advances · 2026Article
- Structural requirements of blood factors binding to soluble hexon trimers with implications for adenovirus cell targeting and immune evasion.PLoS pathogens · 2026Article
- Chimeric Ad5/35 oncolytic adenovirus overcome preexisting neutralizing antibodies and enhance tumor targeting efficiency.Cancer gene therapy · 2025Article
- Article
- Review
- Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT)-Insights from Clinical Cases, In Vitro Studies and Murine Models.Journal of clinical medicine · 2023Review
- Development of Oncolytic Vectors Based on Human Adenovirus Type 6 for Cancer Treatment.Viruses · 2023Article
- Binding of adenovirus species C hexon to prothrombin and the influence of hexon on vector properties in vitro and in vivo.PLoS pathogens · 2022Article
- Cytokine Responses to Adenovirus and Adenovirus Vectors.Viruses · 2022Review
- Infection of non-cancer cells: A barrier or support for oncolytic virotherapy?Molecular therapy oncolytics · 2022Review
- Therapeutic effects of mesenchymal stem cells loaded with oncolytic adenovirus carrying decorin on a breast cancer lung metastatic mouse model.Molecular therapy oncolytics · 2022Article
- The aetiopathogenesis of vaccine-induced immune thrombotic thrombocytopenia.Clinical medicine (London, England) · 2022Review
- ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome.Science advances · 2021Article
- Human AdV-20-42-42, a Promising Novel Adenoviral Vector for Gene Therapy and Vaccine Product Development.Journal of virology · 2021Article
- Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19.Nature communications · 2021Article
- Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2.Science (New York, N.Y.) · 2021Article
- Phospholipidosis is a shared mechanism underlying thebioRxiv : the preprint server for biology · 2021Article
- Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A.Science (New York, N.Y.) · 2021Article
- COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.Research square · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
The development of adenoviral vectors for intravascular (i.v.) delivery will require improvements to their in vivo safety and efficacy. The hypervariable regions (HVRs) of the Ad5 hexon are a target for neutralizing antibodies, but also interact with factor X (FX), facilitating hepatocyte transduction. Ad48, a species D adenovirus, does not bind FX and has low seroprevalence. Therefore, it has been suggested that Ad5HVR48(1-7), a hexon-chimeric vector featuring the seven HVRs from Ad48, should display advantageous properties for gene therapy, by evading pre-existing Ad5 immunity and blocking FX interactions. We investigated the in vivo biodistribution of Ad5, Ad5HVR48(1-7), and Ad48 following i.v. delivery. Ad5HVR48(1-7) displayed reduced hepatocyte transduction and accumulation in Kupffer cells (KCs), but triggered a robust proinflammatory response, even at relatively low doses of vector. We detected elevated serum transaminases (48 hours) and increased numbers of periportal CD11b(+)/Gr-1(+) cells in the livers of Ad5HVR48(1-7)-treated animals following i.v., but not intramuscular (i.m.), delivery. In contrast, Ad48 did not elevate transaminases or result in the accumulation of CD11b(+)/Gr-1(+) cells. Collectively, these findings suggest that substantial hexon modifications can lead to unexpected properties which cannot be predicted from parental viruses. Therefore, refined mutations may be preferential for the successful development of targeted vector systems which require i.v. administration.
Indexed as
Identifiers
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.