Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs

Alonso-Padilla, J., Papp, T., Kaján, G. L., Benkő, M., Havenga, M., Lemckert, A., Harrach, B. and Baker, A. H. (2016) Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs. Molecular Therapy, (doi:10.1038/mt.2015.194) (PMID:26478249) (PMCID:PMC4754553)

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Abstract

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last 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 pre-existing 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew
Authors: Alonso-Padilla, J., Papp, T., Kaján, G. L., Benkő, M., Havenga, M., Lemckert, A., Harrach, B., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Molecular Therapy
Publisher:Nature Publishing Group
ISSN:1525-0016
ISSN (Online):1525-0024
Copyright Holders:Copyright © 2015 Nature Publishing Group
First Published:First published in Molecular Therapy 2015
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
604401Ad-Vec: Adenovirus Vector Technology: Next Generation Systems for Medical TherapyAndrew BakerEuropean Commission (EC)PIAPP-GA-2012-3RI CARDIOVASCULAR & MEDICAL SCIENCES
583361BHF Chair of Translational Cardiovascular SciencesAndrew BakerBritish Heart Foundation (BHF)CH/11/2/28733RI CARDIOVASCULAR & MEDICAL SCIENCES