New strategies for the genetic therapy of primary liver carcinoma

Genetically-based strategies open up new perspectives for the therapy of pr imary liver carcinoma. Suicide genes specifically targeted to hepatoma cell s are able to activate innocuous prodrugs, leading to the toxification of g enetically-modified as well as neighbouring cells (bystander effect). Since serious local and systemic side-effects have to be avoided, in vivo applic ation of this new strategy requires the generation of hepatotropic vector s ystems. Based on the distinct ligand-receptor interaction of Sendai virus F envelope protein, with the liver specific asialoglycoprotein receptor (ASG P-R), we have developed two new ASGP-R restricted viral vector systems: rec ombinant hepatotropic Sendai virus vectors and retroviral MoMLV(SeV-F) pseu dotypes. In combination with hepatoma-specific expression cassettes, curren tly under development, and topical vector application techniques, an effici ent, safe and hepatoma-restricted transfer of therapeutic genes seems to be achievable. New molecular principles, such as the VP22 potentiated bystand er effect, might help to achieve major clinical progress, especially in the adjuvant treatment of microscopic hepatoma nodules.