Recombinant adenoviruses can infect nondividing cells with high efficiency
and are rapidly concentrated in the liver after systemic administration, ma
king them attractive for use in liver-directed gene therapy. How ever, ther
e are two hurdles to clinical application of these vectors. First, adenovir
uses are episomal and have limited life spans within the cell. Second host
antiviral immune responses reduce the duration of vector persistence and pr
eclude long-term transgene expression by repeated injection of the vector S
everal strategies have been designed for abrogation of the specific antiade
noviral immune responses by modification of the host immune system or alter
ation of the vector These strategies and the use of adenoviral vectors for
the treatment of hereditary, infectious, and malignant diseases of the live
r are discussed in this review.