ArticleProceedings of the National Academy of Sciences of the United States of America1999
Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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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.
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Who cites it
147 citing papers in PubMed, 409 citations in OpenAlex.
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- The deLIVERed promises of gene therapy: Past, present, and future of liver-directed gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Strategies for Modifying Adenoviral Vectors for Gene Therapy.International journal of molecular sciences · 2024Review
- Role of homologous recombination/recombineering on human adenovirus genome engineering: Not the only but the most competent solution.Engineering microbiology · 2024Review
- The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine.Viruses · 2023Review
- Gene therapy approaches for equine osteoarthritis.Frontiers in veterinary science · 2022Review
- Intranasal HD-Ad vaccine protects the upper and lower respiratory tracts of hACE2 mice against SARS-CoV-2.Cell & bioscience · 2021Article
- Transfer ofMolecular therapy. Nucleic acids · 2021Article
- Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors.International journal of molecular sciences · 2021Review
- A primer to gene therapy: Progress, prospects, and problems.Journal of inherited metabolic disease · 2021Review
- In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice.Pharmaceutics · 2020Article
- Review
- Retargeting adenoviruses for therapeutic applications and vaccines.FEBS letters · 2020Review
- High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020Review
- A New Gorilla Adenoviral Vector with Natural Lung Tropism Avoids Liver Toxicity and Is Amenable to Capsid Engineering and Vector Retargeting.Journal of virology · 2020Article
- Article
- Innate immunity to adenovirus: lessons from mice.FEBS letters · 2019Review
- No more helper adenovirus: production of gutless adenovirus (GLAd) free of adenovirus and replication-competent adenovirus (RCA) contaminants.Experimental & molecular medicine · 2019Article
- Viral Vector-Based Delivery of CRISPR/Cas9 and Donor DNA for Homology-Directed Repair in an In Vitro Model for Canine Hemophilia B.Molecular therapy. Nucleic acids · 2019Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration of transgene expression, which can be related to immune responses and to toxic effects of viral proteins. In addition, readministration is usually ineffective unless the animals are immunocompromised or a different adenovirus serotype is used. Recently, adenoviral vectors devoid of all viral coding sequences (helper-dependent or gutless vectors) have been developed to avoid expression of viral proteins. In mice, liver-directed gene transfer with AdSTK109, a helper-dependent adenoviral (Ad) vector containing the human alpha(1)-antitrypsin (hAAT) gene, resulted in sustained expression for longer than 10 months with negligible toxicity to the liver. In the present report, we have examined the duration of expression of AdSTK109 in the liver of baboons and compared it to first-generation vectors expressing hAAT. Transgene expression was limited to approximately 3-5 months with the first-generation vectors. In contrast, administration of AdSTK109 resulted in transgene expression for longer than a year in two of three baboons. We have also investigated the feasibility of circumventing the humoral response to the virus by sequential administration of vectors of different serotypes. We found that the ineffectiveness of readministration due to the humoral response to an Ad5 first-generation vector was overcome by use of an Ad2-based vector expressing hAAT. These data suggest that long-term expression of transgenes should be possible by combining the reduced immunogenicity and toxicity of helper-dependent vectors with sequential delivery of vectors of different serotypes.
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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.