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Related Experiment Video

Updated: Jul 6, 2026

Adenovirus-mediated Genetic Removal of Signaling Molecules in Cultured Primary Mouse Embryonic Fibroblasts
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Adenovirus-mediated Genetic Removal of Signaling Molecules in Cultured Primary Mouse Embryonic Fibroblasts

Published on: September 9, 2010

Genetic manipulations of adenovirus type 5 fiber resulting in liver tropism attenuation.

E Vigne1, J-F Dedieu, A Brie

  • 1UMR1582 CNRS/IGR/Aventis, Institut Gustave Roussy, Villejuif, France.

Gene Therapy
|February 7, 2003
PubMed
Summary
This summary is machine-generated.

Modifying adenovirus vectors by shortening fiber shafts or using Ad3 components significantly reduces their ability to infect cells and target organs like the liver. This approach also weakens the host immune response, offering a promising strategy for controlling viral tropism.

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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting

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Last Updated: Jul 6, 2026

Adenovirus-mediated Genetic Removal of Signaling Molecules in Cultured Primary Mouse Embryonic Fibroblasts
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Published on: September 9, 2010

Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches

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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
08:14

Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting

Published on: October 26, 2018

Area of Science:

  • Virology
  • Gene Therapy
  • Molecular Biology

Background:

  • Adenoviral vectors are crucial for gene therapy, but their natural tropism limits targeted delivery.
  • Human adenovirus serotype 5 (Ad5) uses its fiber protein to bind the coxsackie and adenovirus receptor (CAR) for cell entry.
  • Modifying viral tropism requires altering capsid proteins to control cell-specific interactions.

Purpose of the Study:

  • To investigate if genetic modifications to the Ad5 fiber protein can reduce its natural tropism.
  • To assess the impact of fiber shaft shortening (BS1) and fiber pseudo-typing with Ad3 components (DB6) on Ad5 vector binding and transduction.
  • To evaluate the in vivo efficacy and immune response modulation of these modified adenoviral vectors.

Main Methods:

  • Constructed genetically modified adenoviral vectors: BS1 (shortened fiber shaft) and DB6 (Ad3 fiber components).
  • Assessed binding affinity to soluble CAR and CAR-positive cell transduction in vitro.
  • Evaluated in vivo liver transduction by measuring viral DNA and transgene expression after intravenous injection in mice.
  • Monitored host humoral immune response in inoculated animals.

Main Results:

  • Modified vectors (BS1 and DB6) showed a 10-fold decrease in binding to soluble CAR and reduced transduction of CAR-positive cells.
  • BS1 also exhibited impaired interaction with cellular integrins, suggesting steric hindrance.
  • In vivo studies demonstrated a 10-fold reduction in liver transduction (viral DNA and transgene expression) for BS1 and DB6.
  • Both modified vectors elicited a significantly weakened host humoral immune response.

Conclusions:

  • Fiber shortening and pseudo-typing with non-CAR-binding serotypes are effective strategies to attenuate Ad5 vector tropism.
  • These modifications significantly reduce in vitro and in vivo viral transduction, particularly in the liver.
  • The observed weakening of the host immune response suggests potential benefits for repeated administration or reduced immunogenicity.