Viruses 2010, 2(9), 2013-2036; doi:10.3390/v2092013

Improving Adenovirus Based Gene Transfer: Strategies to Accomplish Immune Evasion

1email and 1,2,* email
Received: 9 July 2010; in revised form: 3 September 2010 / Accepted: 15 September 2010 / Published: 24 September 2010
(This article belongs to the Special Issue Adenoviral Vectors)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Adenovirus (Ad) based gene transfer vectors continue to be the platform of choice for an increasing number of clinical trials worldwide. In fact, within the last five years, the number of clinical trials that utilize Ad based vectors has doubled, indicating growing enthusiasm for the numerous positive characteristics of this gene transfer platform. For example, Ad vectors can be easily and relatively inexpensively produced to high titers in a cGMP compliant manner, can be stably stored and transported, and have a broad applicability for a wide range of clinical conditions, including both gene therapy and vaccine applications. Ad vector based gene transfer will become more useful as strategies to counteract innate and/or pre-existing adaptive immune responses to Ads are developed and confirmed to be efficacious. The approaches attempting to overcome these limitations can be divided into two broad categories: pre-emptive immune modulation of the host, and selective modification of the Ad vector itself. The first category of methods includes the use of immunosuppressive drugs or specific compounds to block important immune pathways, which are known to be induced by Ads. The second category comprises several innovative strategies inclusive of: (1) Ad-capsid-display of specific inhibitors or ligands; (2) covalent modifications of the entire Ad vector capsid moiety; (3) the use of tissue specific promoters and local administration routes; (4) the use of genome modified Ads; and (5) the development of chimeric or alternative serotype Ads. This review article will focus on both the promise and the limitations of each of these immune evasion strategies, and in the process delineate future directions in developing safer and more efficacious Ad-based gene transfer strategies.
Keywords: recombinant adenovirus; innate immunity; adaptive immunity; neutralizing antibodies; cellular responses; humoral responses
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MDPI and ACS Style

Seregin, S.S.; Amalfitano, A. Improving Adenovirus Based Gene Transfer: Strategies to Accomplish Immune Evasion. Viruses 2010, 2, 2013-2036.

AMA Style

Seregin SS, Amalfitano A. Improving Adenovirus Based Gene Transfer: Strategies to Accomplish Immune Evasion. Viruses. 2010; 2(9):2013-2036.

Chicago/Turabian Style

Seregin, Sergey S.; Amalfitano, Andrea. 2010. "Improving Adenovirus Based Gene Transfer: Strategies to Accomplish Immune Evasion." Viruses 2, no. 9: 2013-2036.

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