The present invention identifies a protein, designated the
D-sequence-binding protein (D-BP), is phosphorylated at tyrosine residues
and blocks AAV-mediated transgene expression in infected cells by
inhibiting the leading strand viral DNA synthesis. More particularly, the
present invention demonstrates that D-BP is phosphorylated by EGF-R
protein tyrosine kinase. Methods of increasing transcription and
promoting replication of transgenes exploiting this information are
disclosed herein.