ABSTRACT

Adenovirus has shown great potential for gene delivery, exciting a large number of investigators to prepare recombinant vectors bearing therapeutic genes. Adenovirus-based gene delivery systems are the most efficient vectors for gene delivery available to date. The process and the consequences of adenovirus entry into eukaryotic cells is not fully understood at the molecular level. In addition to the deposition of novel nucleic acid in the nucleus of a host cell, the entry of adenovirus can trigger a series of important host responses including the activation of transcription factors involved in inflammatory responses and the initiation of apoptotic responses. The virus must enter the cell by some form of endocytosis, pass across the limiting membrane through the cytoplasm, and enter the nucleus. The adenovirus fiber has long been known as a major determinant of host cell binding. It has been demonstrated that in intact, noninflamed tissue, the transduction efficiency of adenovirus vectors is low.