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Challenges and Prospects for Helper-Dependent Adenoviral Vector-Mediated Gene Therapy

1
Telethon Institute of Genetics and Medicine, Naples 80131, Italy
2
Department of Translational Medicine, Federico II University of Naples, Naples 80131, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2014, 2(2), 132-148; https://doi.org/10.3390/biomedicines2020132
Received: 6 February 2014 / Revised: 7 March 2014 / Accepted: 18 March 2014 / Published: 2 April 2014
(This article belongs to the Special Issue Gene Therapy Used in Cancer Treatment)
Helper-dependent adenoviral (HDAd) vectors that are devoid of all viral coding sequences are promising non-integrating vectors for gene therapy because they efficiently transduce a variety of cell types in vivo, have a large cloning capacity, and drive long-term transgene expression without chronic toxicity. The main obstacle preventing clinical applications of HDAd vectors is the host innate inflammatory response against the vector capsid proteins that occurs shortly after intravascular vector administration and result in acute toxicity, the severity of which is dose dependent. Intense efforts have been focused on elucidating adenoviral vector–host interactions and the factors involved in the acute toxicity. This review focuses on the recent acquisition of data on such interactions and on strategies investigated to improve the therapeutic index of HDAd vectors. View Full-Text
Keywords: adenovirus; helper-dependent adenoviral vectors; gutless vectors; liver directed gene therapy adenovirus; helper-dependent adenoviral vectors; gutless vectors; liver directed gene therapy
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Piccolo, P.; Brunetti-Pierri, N. Challenges and Prospects for Helper-Dependent Adenoviral Vector-Mediated Gene Therapy. Biomedicines 2014, 2, 132-148.

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