CONSTRUCTION OF AN ADENOVIRUS TYPE 7A E1A(-) VECTOR

A strategy for constructing replication-defective adenovirus vectors f rom non-subgroup C viruses has been successfully demonstrated with ade novirus type 7 strain a (Ad7a) as the prototype. An E1A-deleted Ad7a r eporter virus expressing the chloramphenicol acetyltransferase (CAT) g ene from the cytomegalovirus promoter enhancer was constructed with DN A fragments isolated from Ad7a, an Ad7a recombination reporter plasmid , and the 293 cell line. The Ad7a-CAT virus particle transduces A549 c ells as efficiently as Ad5-based vectors. Intravenous infections in a murine model indicate that the Ad7a-CAT virus infects a variety of tis sues, with maximal levels of CAT gene expression found in the liver. T he duration of Ad7a-CAT transgene expression in the liver was maximall y maintained 2 weeks postinfection, with a decline to baseline activit y by the week 4 postinfection. Ad7a-CAT represents the first example o f a non-subgroup C E1A(-) adenovirus gene transfer vector.