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A partial E3 deletion in replication-defective adenoviral vectors allows for stable expression of potentially toxic transgene products.

A partial E3 deletion in replication-defective adenoviral vectors allows for stable expression of potentially toxic transgene products.
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Haut LH, Gill AL, Kurupati RK, Bian A, Li Y, Giles-Davis W, Xiang Z, Zhou X, Ertl HC,


Haut LH, Gill AL, Kurupati RK, Bian A, Li Y, Giles-Davis W, Xiang Z, Zhou X, Ertl HC, (click to view)

Haut LH, Gill AL, Kurupati RK, Bian A, Li Y, Giles-Davis W, Xiang Z, Zhou X, Ertl HC,

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Human gene therapy methods 2016 9 7()

Abstract

Adenovirus (Ad) is used extensively for construction of viral vectors, most commonly with deletion in its E1 and/or E3 genomic regions. Previously, our attempts to insert Env proteins of HIV-1 into such vectors based on chimpanzee-derived Ad (AdC) viruses were thwarted. Here, we describe that genetic instability of an E1- and E3-deleted AdC vector of serotype C6 expressing envelope (Env) protein of HIV-1 can be overcome by reinsertion of E3 sequences with anti-apoptotic activities. This partial E3 deletion presumably delays premature death of HEK-293 packaging cell lines due to Env-induced cell apoptosis. The same partial E3 deletion also allows for the generation of stable gp140- and gp160-expressing Ad vectors based on AdC7, a distinct AdC serotype. Env-expressing AdC vectors containing the partial E3 deletion are genetically stable upon serial cell culture passaging, produce yields comparable to those of other AdC vectors, and induce transgene product-specific antibody responses in mice. A partial E3 deletion thereby allows expansion of the repertoire of transgenes that can be expressed by Ad vectors.

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