The present invention features helper-dependent adenoviral vector
elements, and helper adenoviral elements, that enhance the production and
isolation of helper-dependent adenoviral vectors. Such elements include a
modified packaging signal having low homology to, and preferably less
activity than, a wild-type packaging signal, an E4 non-coding segment
directly joined to the 5' ITR that confers a selective advantage, and
stuffer region(s) that provide a helper-dependent adenoviral vector with
a GC content of about 50% to about 60%. The modified packaging signal is
preferably used in a helper virus to decrease recombination and
generation of the virus. The E4 non-coding segment and the stuffer
region(s) are preferably used in a helper-dependent adenoviral vector to
provide the vector with a growth advantage over a helper virus.