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The Open Gene Therapy Journal
Article . 2009 . Peer-reviewed
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Assessment of Genetic Shielding for Adenovirus Vectors

Authors: Hui-Chen Hsu; Myunghee Kim; Jian Chen; Imre Kovesdi; Aleksandr Krendelshchikov; David T. Curiel; Susan J. Hedley; +1 Authors

Assessment of Genetic Shielding for Adenovirus Vectors

Abstract

Development of adenovirus (Ad) vectors in the clinical context has highlighted that vector efficacy may be limited by the host humoral response due to pre-existing titers of neutralizing antibodies against the vector itself in humans. Further, multiple dosing of Ad vectors based on serotype 5 would be limited. Current immune evasion strategies being investigated by other laboratories are only applicable to non-replicating vectors. Therefore we have proposed ge- netic shielding as an alternate that would be applicable to both non-replicating and conditionally replicating Ad vectors. Genetic shielding would encapsulate fusion of a self-protein to Ad minor capsid protein, pIX, as a means to cloak immu- nogenic capsid epitopes and prevent neutralization of Ad vectors through Ad specific antibodies. In the development of a suitably shielded Ad vector we choose several self-proteins that we attempted to fuse to pIX. We have also used an indirect method to conjugate albumin to the capsid through an albumin binding domain fused to pIX. Despite attaining novel pIX modified Ad vectors we found that none of the pIX attached molecules in this study prevented neutralizing an- tibodies from halting gene transfer.

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
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