ing 6-8 hours later) (Figure 2.2-A). The early phase genes are grouped as 
Ela, Elb , E2a, E2b, E3 and E4. Part of the LI region is also grouped as an 
"early" phase gene. Regions active in both the early and late phase in- 
clude E2a, E2b, and IX. The late phase genes are grouped as part of LI, L2 , 
L3, L4, and L5 . Also in the late phase there is transcription of regions 
IVa2 and VA. 
The early region genes code for at least 30 mRNA transcripts. Specific 
functions have been defined for many, but not all of the proteins coded by 
these transcripts (see Pettersson, 1984 for details) . The El products are 
the first adenovirus proteins generated post- infection and function as 
important transcriptional regulators. Importantly, most of the El region 
sequences are critical for viral replication; by removing the Ela region 
and a substantial part of Elb, the virus can be rendered replication defi- 
cient. The E3 region can be deleted with no apparent effect on viral growth 
in culture (see section 4.8 for a discussion of this region and the safety 
aspects of deleting E3 sequences) . 
The late region genes are mostly related to production of the structural 
proteins required for assembly of the nucleoprotein core (e.g. the genomic 
DNA of the virus plus the proteins associated with the DNA) and the capsid 
forming the outer shell of the virus (Ginsberg, 1984; Horwitz, 1990a). The 
five families of late mRNAs (Ll-5) all use the same tripartite leader 
sequences 1, 2, and 3 found 5' to the L region genes (Figure 2.2-A). 
Besides the early and late regions genes, other important regions of the 
adenovirus genome include the left and right inverted terminal repeats 
(ITR) , and sequences required for initiating replication and encapsidation 
(VO of the virus. 
2.2.1 Structural Proteins 
Each adenovirus virion has approximately 2,700 polypeptides. The vast 
majority of these are the structural proteins, most of which comprise 
either the capsid or are associated with both the capsid and the nucleopro- 
tein core (Table 2.2.1-A). Analysis of the purified adenovirus AdCFTR by 
sodium dodecyl sulfate acrylamide gels reveals the same major structural 
proteins found in replication competent Ad5 (P. Seth, R. Crystal, not 
shown). For details as to the structure, location, function and assembly of 
these proteins, see Pettersson, 1984. 
2.3 Structure of the Replication Deficient, Recombinant Adenovirus Vec- 
tors 
The replication deficient, recombinant adenovirus vector AvlCFl is based on 
the genome of human adenovirus type 5 . The naturally occurring Ad5 has a 
double stranded DNA genome of 35,935 bp (GenBank accession No. M73260) . The 
overall structure of AdCFTR has been published (see Appendix 1) . AvlCFl has 
a genome of 36,397 bp. As with AdCFTR, AvlCFl has two major structural 
deletions (relative to Ad5) , an El deletion (1.26-9.24 mu of Ad5) and an E3 
deletion (78.5-84.7 mu of Ad5) . Also idential to AdCFTR, AvlCFl has a minor 
2 bp deletion in the VA-I promoter (see appendix 3) . The overall structure 
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