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Updated: Jul 14, 2026
Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
Published on: August 13, 2013
Different modulation of cellular transcription by adenovirus 5, DeltaE1/E3 adenovirus and helper-dependent vectors
Yuri Martina1, Daniele Avitabile, Stefania Piersanti
1Department of Genetics and Molecular Biology, University La Sapienza, and Fondazione Parco Biomedico S. Raffaele, Rome, Italy.
Abstract:
One problem encountered in the use of adenoviral vectors for gene therapy is their toxicity. Although many studies have analyzed this question in vivo, few researches have investigated adenovirus vector effects at the cellular level using a large-scale approach. In particular, no such data are available for helper-dependent adenovirus vectors (HD), which are promising adenovirus vectors for clinical applications since they are devoid of all viral genes and can host large transgene cassettes. The present study used gene chips to examine (Affymetrix HG-U95Av2 interrogating 12,626 unique human transcripts) the effect on liver cells of HD vectors versus that of DeltaE1/E3 adenovirus vector and wild type Adenovirus (Ad5). The effects of the DeltaE1/E3 adenovirus and of HD vectors were comparable, and significantly milder than that of Ad5. Interestingly the expression signatures of DeltaE1/E3 adenovirus and HD vectors were non-overlapping both at the single gene and the pathway level, suggesting specific and different interactions between the host cell and the two gene therapy vectors.
Insights
Helper-dependent adenovirus vectors (HD) show milder toxicity in liver cells compared to wild-type Adenovirus (Ad5). Gene chip analysis revealed distinct cellular responses to HD and DeltaE1/E3 vectors, suggesting specific host-vector interactions for gene therapy.
Area of Science:
- Molecular Biology
- Gene Therapy
- Virology
Background:
- Adenoviral vectors are used in gene therapy but exhibit toxicity.
- In vivo toxicity studies are common, but cellular-level investigations using large-scale approaches are limited.
- Helper-dependent adenovirus vectors (HD) are promising for clinical use due to their reduced viral components and capacity for large transgenes.
Purpose of the Study:
- To investigate the cellular effects of helper-dependent adenovirus vectors (HD) compared to other adenovirus types.
- To analyze gene expression profiles in liver cells exposed to HD vectors, DeltaE1/E3 adenovirus, and wild-type Adenovirus (Ad5) using a large-scale approach.
- To determine if HD vectors exhibit different cellular interactions than other adenovirus vectors.
Main Methods:
- Utilized gene chips (Affymetrix HG-U95Av2) to examine the expression of 12,626 unique human transcripts.
- Exposed liver cells to helper-dependent adenovirus vectors (HD), DeltaE1/E3 adenovirus vector, and wild-type Adenovirus (Ad5).
- Compared gene expression signatures at both single gene and pathway levels.
Main Results:
- The cellular effects of DeltaE1/E3 adenovirus and HD vectors were comparable and significantly milder than those of wild-type Adenovirus (Ad5).
- Expression signatures for DeltaE1/E3 adenovirus and HD vectors were non-overlapping.
- Differences were observed at both the single gene and pathway levels, indicating distinct host-cell interactions.
Conclusions:
- HD vectors and DeltaE1/E3 adenovirus vectors demonstrate reduced cellular toxicity compared to wild-type Adenovirus (Ad5).
- The distinct expression signatures suggest that HD and DeltaE1/E3 vectors engage in specific and different interactions with host cells.
- These findings support the potential of HD vectors for safer gene therapy applications.
