Method of using adenoviral vectors with increased persistence in vivo

A method of expressing an exogenous nucleic acid in a mammal, wherein the method comprises slowly delivering to the bloodstream of the mammal a dose of a replication-deficient or conditionally-replicating adenoviral vector having reduced ability to transduce mesothelial cells and hepatocytes compared to wild-type adenoviral vector and comprising an exogenous nucleic acid,

• wherein the normalized average bloodstream concentration of the replication-deficient or conditionally-replicating adenoviral vector over a time period of 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, wherein the method comprises slowly delivering a dose of a replication-deficient or conditionally-replicating adenoviral vector to the bloodstream comprising (a) a nucleic acid sequence encoding a tumoricidal agent and (b) an adenoviral fiber protein which does not mediate adenoviral entry via a coxsackievirus and adenovirus receptor (CAR), such that the tumoricidal agent is produced and tumor cells in the mammal are destroyed.

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.