Vectors with Additional Early Gene Deletions

First-generation Ad vectors permit limited Ad gene expression and DNA replication, which probably contributes to the immune response against the vector. In addition, the possibility of making RCA during propagation is a potentially dangerous feature. By making additional mutations or deletions in the Ad genome, both of these problems can be avoided. One implementation is to make an E1" vector with an E2A mutation that renders the vector replication incompetent at 37°C (90). Such temperature-sensitive vectors can be propagated at 32°C but cannot replicate in the mammalian host at 37°C, even if E1-like activities are present. Further, if homologous recombination in 293 cells during production results in a E1 + viral genome, the ability to replicate in a mammalian host is not restored. In vivo studies show that this defect reduces the inflammatory response following vector administration and

Table 1 Adenovirus Deletions and Complementing Cell Lines
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