Adenovirus (Adv) is double-stranded DNA (dsDNA) virus, belong to the Adenoviridae family, adenovirus vector is derived from Adv, have been frequently used for recombinant protein expression in mammalian cells and for applications in gene therapy. Adenovirus are capable of infecting a broader variety of cells, including those that have a comparatively slow rate of cell division. When adenoviruses infect a host cell, their genetic material (DNA) is not incorporated into the host’s genome and left free in the nucleus in the form of an extrachromosomal gene segment, which is also known as an episome. Their extrachromosomal location prevents germline gene transfer and also eliminates the risk of cancer due to insertional mutagenesis.

During the years adenovirus vectors have seen a multitude of improvements including engineering of gutless vectors with deletions in the E1-4 genes to reduce the vector toxicity and increase packaging capacity(~35 kb). The E1 gene products, E1A and E1B, are involved in the replication of the virus. The E2 proteins provide the machinery for viral DNA replication and facilitate transcription of late genes. Most of the E3 proteins are involved in modulating the host’s immune response. The E4 gene products are involved in the metabolism of virus messenger RNA (mRNA), promotion of viral DNA replication and in shutting-off of host protein synthesis. Adenovirus vector have commonly been subjected to several preclinical and clinical trials. Engineering of packaging cell lines for adenovirus vector have significantly facilitated virus production.

Adenovirus vector advantages

Easily manipulated in laboratory setting

High expression of transgene

Broad tropism, including DC

No risk of insertional mutagenesis

Many strains available

Replication-deficient strains used, limiting pathogenicity

Reference:

Viral Vector –based Therapeutic Cancer Vaccines. Cecilia Larocca, B.S. and Jeffrey Schlom, Ph.D. Cancer J. 2011 September ; 17(5): 359–371.

Viral Vector-Based Cancer Immunotherapy. Lundstrom K. Viral Vector-Based Cancer Immunotherapy. Austin Immunol. 2016; 1(2): 1008.