Adenovirus: from foe to friend.
Human adenoviruses (HAdVs) can cause mild respiratory, gastrointestinal, urogenital and ocular disease. Knowledge about HAdVs has been expanding for more than five decades putting them amongst the most-studied viruses. This continued interest stems, to a great extent, from the fact that these double-stranded DNA viruses have proven to be a versatile tool to probe the basic phenomena of eukaryotic cells. HAdV research has led to the discovery of, for instance, RNA splicing and greatly contributed to our knowledge of processes as fundamental as replication, transcription and translation. Moreover, the transformation of rodent cells by HAdVs has provided a system to unravel the molecular pathways that control cell proliferation. As a result, the genetic organisation of these agents is known in great detail allowing the straightforward manipulation of their genomes. In addition, the virus itself became renowned for its ability to produce large amounts of progeny and to efficiently infect mammalian cells regardless of their cell cycle status. These features contributed to the broad use of recombinant HAdVs as gene carriers particularly in in vivo settings where the vast majority of target cells are post-mitotic. The most advanced type of HAdV vectors can accommodate up to 37 kb of foreign DNA and are devoid of viral genes. With the aid of these high-capacity HAdV vectors large physiologically responsive transcriptional elements and/or genes can be efficiently introduced into target cells while minimising adaptive immune responses against the transduced cells. This article provides information on HAdV especially on the aspects pertinent to the design, production and performance of its recombinant forms. The development and characteristics of the main HAdV-based vector types are also briefly reviewed.
Gonçalves
Manuel A F V
MA
Gene Therapy Section, Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands. m.goncalves@lumc.nl
de Vries
Antoine A F
AA
D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections / Q000821:virology*; D001483:Base Sequence; D002986:Clinical Trials as Topic; D005822:Genetic Vectors; D016679:Genome, Viral / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data