English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Preclinical arterial gene transfer studies with adenoviral vectors are typically performed in laboratory animals that lack immunity to adenovirus. However, human patients are likely to have prior exposures to adenovirus that might affect: (a) the success of arterial gene transfer; (b) the duration of recombinant gene expression; and (c) the likelihood of a destructive immune response to transduced cells. We confirmed a high prevalence (57%) in adult humans of neutralizing antibodies to adenovirus type 5. We then used a rat model to establish a central role for the immune system in determining the success as well as the duration of recombinant gene expression after adenovirus-mediated gene transfer into isolated arterial segments. Vector-mediated recombinant gene expression, which was successful in naive rats and prolonged by immunosuppression, was unsuccessful in the presence of established immunity to adenovirus. 4 d of immunosuppressive therapy permitted arterial gene transfer and expression in immune rats, but at decreased levels. Ultraviolet-irradiated adenoviral vectors, which mimic advanced-generation vectors (reduced viral gene expression and relatively preserved capsid function), were less immunogenic than were nonirradiated vectors. A primary exposure to ultraviolet-irradiated (but not nonirradiated) vectors permitted expression of a recombinant gene after redelivery of the same vector. In conclusion, arterial gene transfer with current type 5 adenoviral vectors is unlikely to result in significant levels of gene expression in the majority of humans. Both immunosuppression and further engineering of the vector genome to decrease expression of viral genes show promise in circumventing barriers to adenovirus-mediated arterial gene transfer.

the journal of clinical investigation/the journal of clinical investigation

Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries. Potential for immunosuppression and vector engineering to overcome barriers of immunity.