Different modulation of cellular transcription by adenovirus 5, ΔE1/E3 adenovirus and helper-dependent vectors

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 ΔE1/E3 adenovirus vector and wild type Adenovirus (Ad5). The effects of the ΔE1/E3 adenovirus and of HD vectors were comparable, and significantly milder than that of Ad5. Interestingly the expression signatures of ΔE1/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.