The baculovirus vector system for gene delivery into hepatocytes

Gene therapy in the liver requires powerful vectors capable of mediating sufficient gene delivery and expression in affected hepatocytes. Viral vectors are amongst the most efficient tools for gene delivery, and the search for tissue-specific infecting viruses is important for the development of in v i v o gene therapy strategies. We have recently shown for the first time that a genetically modified baculovirus Autographa californica can efficiently and specifically transfer genes into cultured l iver ce l l s from various origin. The efficiency of baculovirus-mediated gene transduction into hepatocytes was determined to approach 100% using appropriate virus titers. Apart from these features, potential advantages of baculovirus vectors are the nearly unlimited capacity for insertion of foreign DNA, a supposed restrict ion of viral promoters to the arthropod host and the ease of generating high vector titers. Uptake of the virus occurs via the endosomal pathway, most l ikely via a receptor that i s currently under investigation. Baculovirus-mediated gene expression i s transient in dividing cel ls , but prolonged expression can be achieved in non-dividing primary hepatocytes. Baculovirus-mediated gene transfer i s feasible into ex v i v o perfused human liver tissue. Systemic application of baculovirus vectors i n v i v o i s hampered by the complement (C) system. Current attempts to facilitate baculovirus-mediated gene transfer i n v i v o include strategies for both, blocking or avoiding the C system and generation of new baculovirus vectors that are not affected by the C system. Alternatively, direct injection of baculovirus vectors was successful into normal mouse l iver and into induced human hepatocarcinomas in nude mice. The potential of baculovirus vectors in v i tro and the feasibility of vector application i n v i v o provide the basis for gene therapy strategies for metabolic diseases and tumors of the liver.