Abstract
E1-deleted adenovirus (Ad) vectors expressing the human coagulation factor IX (hFIX) or the bacterial β-galactosidase (lacZ) were injected intravenously into various strains of immunocompetent (C57Bl/6, BALB/c, CD1, CBA/J, C3H) and immunodeficient (BALB/c-nu/nu, C57Bl/6-nu/nu, SCID, NIH-bg-nu-xid) mice. Regular analysis of mouse sera and tissues showed a persistent expression of both transgenes in immunodeficient mice, while detection diminished very rapidly in immunocompetent mice. The mechanisms responsible for the transient detection of the two transgenes were however not identical. Rapid decline of lacZ expression was correlated with a rapid decrease of viral DNA sequences, and consequently to the induction of a cellular immune response to the lacZ antigen. In contrast, absence of detectable levels of serum hFIX in immunocompetent animals was not associated with a loss of viral DNA but was strictly correlated with the induction of anti-hFIX antibodies. Surprisingly, anti-hFIX antibodies were never detected in C57Bl/6 mice, leading to prolonged detection of hFIX. These results suggest that cellular immunity to viral antigens plays a minor role in the early extinction of transgene expression and illustrate the influence of the cellular (eg lacZ) or humoral (eg hFIX) immunity to transgene-encoded products on the persistence of transgene expression.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Michou, A., Santoro, L., Christ, M. et al. Adenovirus-mediated gene transfer: influence of transgene, mouse strain and type of immune response on persistence of transgene expression. Gene Ther 4, 473–482 (1997). https://doi.org/10.1038/sj.gt.3300412
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.gt.3300412
Keywords
This article is cited by
-
Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction
Scientific Reports (2017)
-
Hybrid Nonviral/Viral Vector Systems for Improved piggyBac DNA Transposon In Vivo Delivery
Molecular Therapy (2015)
-
Gene therapy: light is finally in the tunnel
Protein & Cell (2011)
-
Absence of Systemic Immune Response to Adenovectors After Intraocular Administration to Children With Retinoblastoma
Molecular Therapy (2010)
-
BALB/c Mice Show Impaired Hepatic Tolerogenic Response Following AAV Gene Transfer to the Liver
Molecular Therapy (2010)