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Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors

Lopez-Gordo, Estrella; Podgorski, Iva I.; Downes, Nicholas; Alemany, Ramon (2014) Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors. Human Gene Therapy, 25 (4). pp. 285-300. ISSN 1043-0342

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Adenoviruses are efficient gene delivery vectors based on their ability to transduce a wide variety of cell types and drive high-level transient transgene expression. While there have been advances in modifying human adenoviral (HAdV) vectors to increase their safety profile, there are still pitfalls that need to be further addressed. Preexisting humoral and cellular immunity against common HAdV serotypes limits the efficacy of gene transfer and duration of transgene expression. As an alternative, nonhuman AdV (NHAdV) vectors can circumvent neutralizing antibodies against HAdVs in immunized mice and monkeys and in human sera, suggesting that NHAdV vectors could circumvent preexisting humoral immunity against HAdVs in a clinical setting. Consequently, there has been an increased interest in developing NHAdV vectors for gene delivery in humans. In this review, we outline the recent advances and limitations of HAdV vectors for gene therapy and describe examples of NHAdV vectors focusing on their immunogenicity, tropism, and potential as effective gene therapy vehicles.

Item Type: Article
Additional Information: We would like to thank all members of the "ADVance" international training network (Adenoviruses as Clinical Treatments; FP7 ITN, EU grant agreement ref. 290002) and in particular Andrew Baker and Eric J. Kremer for their advice and encouragement to write this review.
Uncontrolled Keywords: efficient gene-transfer; neutralizing antibodies target; preexisting anti-Ad5 immunity; plasmacytoid dendritic cells; infectious bursal disease; acute respiratory-disease; full-length dystrophin; growth-factor receptor; lethal orphan virus; human-derived cells
Subjects: NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
NATURAL SCIENCES > Biology > Microbiology
Depositing User: Iva Škrinjar
Date Deposited: 22 Nov 2019 11:50
DOI: 10.1089/hum.2013.228

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