Immune responses to transgene–encoded proteins limit the stability of gene expression after injection of replication–defective adenovirus vectors View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-05

AUTHORS

S K Tripathy, H B Black, E Goldwasser, J M Leiden

ABSTRACT

The use of replication-defective adenoviruses (RDAd) for human gene therapy has been limited by host immune responses that result in transient recombinant gene expression in vivo. It remained unclear whether these immune responses were directed predominantly against viral proteins or, alternatively, against foreign transgene-encoded proteins. In this report, we have compared the stability of recombinant gene expression in adult immunocompetent mice following intramuscular (i.m.) injection with identical RDAd encoding self (murine) or foreign (human) erythropoietin. Our results demonstrate that immune responses direct against foreign transgene-encoded proteins are the major determinants of the stability of gene expression following i.m. injection of RDAd. Moreover, we demonstrate long-term recombinant gene expression in immunocompetent animals following a single i.m. injection of RDAd encoding a self protein. These findings are important for the design of future preclinical and clinical gene therapy trials. More... »

PAGES

545-550

Journal

TITLE

Nature Medicine

ISSUE

5

VOLUME

2

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm0596-545

DOI

http://dx.doi.org/10.1038/nm0596-545

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016176325

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8616713


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