title: Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5-based Constructs.
abstract: Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in preclinical models and clinical trials over the past two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread preexisting immunity have been shown to significantly impede the effectiveness of HAdV-5-mediated gene transfer. It is therefore that the in-depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Julio
authors.initials: J
authors.lastname: Alonso-Padilla
authors.affiliation: Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Papp
authors.affiliation: Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Győző L
authors.initials: GL
authors.lastname: Kaján
authors.affiliation: Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Benkő
authors.affiliation: Batavia Biosciences B.V., Leiden, The Netherlands.
authors.forename: Menzo
authors.initials: M
authors.lastname: Havenga
authors.affiliation: Batavia Biosciences B.V., Leiden, The Netherlands.
authors.forename: Angelique
authors.initials: A
authors.lastname: Lemckert
authors.affiliation: Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Harrach
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.|Current address: Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000276:immunology / Q000633:toxicity*; D006801:Humans; D007113:Immunity, Innate