Biology of Adenovirus and Its Use as a Vector for Gene Therapy

Engineering the Rapid Adenovirus Production and Amplification (RAPA) Cell Line to Expedite the Generation of Recombinant Adenoviruses

“…Human adenovirus serotype 5 (Ad5) contains a linear 36 kb double-stranded genome [1, 2]. The adenovirus virion is a nonenveloped icosahedral particle about 70–90 nm in size with an outer protein shell surrounding an inner nucleoprotein core [2].…”

“…The adenovirus virion is a nonenveloped icosahedral particle about 70–90 nm in size with an outer protein shell surrounding an inner nucleoprotein core [2]. Recombinant replication-deficient adenoviruses are usually missing critical viral functions leading to 1) the inhibition of viral spreading that renders such viruses safe and 2) the insertion of foreign transgenes, secondary to the packaging space created by the deletion of viral genes [3, 4].…”

“…Recombinant adenoviruses offer several attractive features for gene transfer, including a large capacity for gene delivery, an efficient production of high titer viral stocks, high levels of transgene expression and the ability to transduce a wide range of mammalian tissues and dividing/non-dividing cells [4, 5]. Additionally, adenovirus-mediated gene delivery does not involve DNA integration into host genome so the risk of insertional mutagenesis is low [2, 4]. The utility of recombinant adenoviruses has further been benefited from the fact that the mechanisms underlying adenovirus DNA replication and adenovirus life cycle have been well studied [1, 2, 4].…”

“…Additionally, adenovirus-mediated gene delivery does not involve DNA integration into host genome so the risk of insertional mutagenesis is low [2, 4]. The utility of recombinant adenoviruses has further been benefited from the fact that the mechanisms underlying adenovirus DNA replication and adenovirus life cycle have been well studied [1, 2, 4]. …”

“…For the past decades, recombinant adenovirus technologies have gone through rather extensive evolutions that led to the development of several generations of adenoviral vectors, including the most drastic form of gutless high-capacity adenoviral vector [2, 4]. The first-generation recombinant adenoviral vectors, which are most commonly used adenoviruses, usually have both the E1 and E3 regions deleted [1, 4].…”