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A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo.

Publication ,  Journal Article
Zhu, J; Huang, X; Yang, Y
Published in: Molecular therapy : the journal of the American Society of Gene Therapy
July 2008

Recombinant adenoviruses have been used widely for gene therapy due to their high transduction efficiency in vivo. However, the attendant innate immune response to adenoviral vectors has limited their applications for in vivo gene therapy. Recent studies have shown that adenoviruses activate the innate immunity through both Toll-like receptor-dependent (TLR-dependent) and TLR-independent pathways, leading to the production of type I interferons (IFNs) and other inflammatory cytokines. Furthermore, type I IFNs play a pivotal role in innate immune elimination of adenoviral vectors in vivo. It remains to be defined how type I IFNs regulate innate immune clearance of adenoviral vectors. In this study, we showed in vivo that natural killer (NK) cells were activated and accumulated in the liver upon intravenous administration of adenoviral vectors, leading to the loss of adenoviral genome and the reduction of transgene expression. We further demonstrated that type I IFNs were critical for the activation of NK cells. This was achieved by direct action of type I IFNs on NK cells. Overall, our observations reveal a critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo and may help design effective strategies to improve the outcome of adenovirus-mediated gene therapy.

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Published In

Molecular therapy : the journal of the American Society of Gene Therapy

DOI

EISSN

1525-0024

ISSN

1525-0016

Publication Date

July 2008

Volume

16

Issue

7

Start / End Page

1300 / 1307

Related Subject Headings

  • Transgenes
  • Mice, Mutant Strains
  • Mice
  • Lymphocyte Activation
  • Liver
  • Killer Cells, Natural
  • Interferon Type I
  • Immunity, Innate
  • Genetic Vectors
  • Genetic Therapy
 

Citation

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Zhu, J., Huang, X., & Yang, Y. (2008). A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo. Molecular Therapy : The Journal of the American Society of Gene Therapy, 16(7), 1300–1307. https://doi.org/10.1038/mt.2008.88
Zhu, Jiangao, Xiaopei Huang, and Yiping Yang. “A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo.Molecular Therapy : The Journal of the American Society of Gene Therapy 16, no. 7 (July 2008): 1300–1307. https://doi.org/10.1038/mt.2008.88.
Zhu J, Huang X, Yang Y. A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo. Molecular therapy : the journal of the American Society of Gene Therapy. 2008 Jul;16(7):1300–7.
Zhu, Jiangao, et al. “A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo.Molecular Therapy : The Journal of the American Society of Gene Therapy, vol. 16, no. 7, July 2008, pp. 1300–07. Epmc, doi:10.1038/mt.2008.88.
Zhu J, Huang X, Yang Y. A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo. Molecular therapy : the journal of the American Society of Gene Therapy. 2008 Jul;16(7):1300–1307.

Published In

Molecular therapy : the journal of the American Society of Gene Therapy

DOI

EISSN

1525-0024

ISSN

1525-0016

Publication Date

July 2008

Volume

16

Issue

7

Start / End Page

1300 / 1307

Related Subject Headings

  • Transgenes
  • Mice, Mutant Strains
  • Mice
  • Lymphocyte Activation
  • Liver
  • Killer Cells, Natural
  • Interferon Type I
  • Immunity, Innate
  • Genetic Vectors
  • Genetic Therapy