Method of using adenoviral vectors with increased persistence in vivo

摘要

The invention provides a method of expressing an exogenous nucleic acid in a mammal. The method comprises slowly releasing into the bloodstream a dose of replication-deficient or conditionally-replicating adenoviral vector having reduced ability to transduce mesothelial cells and hepatocytes. The normalized average bloodstream concentration of the adenovirus over 24 hours post-administration is at least about 1%. Alternatively, the normalized average bloodstream concentration over 24 hours post-administration is at least about 5-fold greater than the normalized average bloodstream concentration for an equivalent dose of a wild-type adenoviral vector. A method of destroying tumor cells in a mammal also is provided, as is a replication-deficient adenoviral vector comprising a serotype 5 or serotype 35 adenoviral genome with a serotype 41 fiber protein, wherein the replication-deficient adenoviral vector exhibits reduced native binding to integrins.