However, despite these advantages the clinical use of Ad-based vectors in virotherapy and gene therapy still faces several hurdles. They can efficiently infect both dividing and quiescent cells, and the availability of scalable production systems enables large-scale vector production to high titers. The recent success of Ad vectors in clinical trials is based on numerous advantageous features: Ad-based vectors exhibit broad tropism profiles, have large packaging capacities (up to ~36 kb), and persist episomally in infected cells. Penton consists of homopentamers of penton-base proteins located on each icosahedral edge (vertex) forming the base for the vertex’s spike that consists of trimers of glycosylated fiber protein. Twelve hexon homotrimers form one capsid facet, of which 20 are present in the capsid. Of these major capsid proteins, hexon is both the largest and most abundant protein of the shell. The viral capsid is composed of three major capsid proteins (hexon, penton base, and fiber) and four minor proteins (IIIa, VI, VIII, and IX) that are organized in icosahedral symmetry. The human Ad has a ~38 kb double-stranded DNA genome. During the ongoing global SARS-CoV2 pandemic, Ad-based vaccines were successfully tested in clinical trials, were approved as vaccines against COVID-19, and are being used as efficacious preventive vaccines. Adenovirus (Ad) vectors are the most frequently used vectors in gene therapy trials and are currently mainly applied in cancer therapies (reviewed in ) and as novel vaccines (reviewed in ).
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