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

Julio Alonso-Padilla, Tibor Papp, Gyozo L. Kaján, Mária Benko, Menzo Havenga, Angelique Lemckert, Balázs Harrach, Andrew H. Baker

Research output: Contribution to journalReview article

46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6-16
Number of pages11
JournalMolecular Therapy
Volume24
Issue number1
DOIs
Publication statusPublished - Feb 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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