The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: Toward realistic long-term neurological gene therapy for chronic diseases
Open accessAbstract
Although adenoviral vectors provide prolonged gene expression in the brain by comparison to peripheral organs, expression is eliminated by a severe inflammatory infiltration (i.e., activated macrophages/microglia and T-lymphocytes) after peripheral infection with adenovirus. Here, we demonstrate that high-capacity adenoviral (HC-Ad) vectors succeed in maintaining long-term transgene expression in the brain, even in the presence of an active peripheral immunization with adenovirus that completely eliminates expression from first-generation vectors within 60 days. Importantly, even 60 days after the peripheral infection, brains injected with first-generation vectors exhibited evidence of a chronic infiltration of CD8 + cells, macrophage/microglial activation, and up-regulation of brain MHC-I expression. No inflammation was observed in the brains injected with the HC-Ad vector. Thus, these results demonstrate that HC-Ad vectors will allow safe, stable, and long-term transgene expression in the brain, even in the presence of peripheral infection with adenovirus. This markedly improves the prospects for the use of adenoviral vectors for long-term gene therapy of neurological disorders.
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Cites
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Progress and problems with the use of viral vectors for gene therapy
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Metadata
- Authors
- Thomas, C. E., Schiedner, G., Kochanek, S., Castro, M. G., & Löwenstein, P. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-06-06
- Volume
- 97
- Issue
- 13
- Pages
- 7482-7487
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2042834453
- Cited by
- 253
- References
- 23
- FWCI
- 15.03
- Type
- journal article
- Language
- en
- Open access
- green
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- Thomas, C. E., Schiedner, G., Kochanek, S., Castro, M. G., & Löwenstein, P. R. (2000). Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: Toward realistic long-term neurological gene therapy for chronic diseases. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.120474397
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