A Review of Nonviral Gene Therapy for the Liver

Abstract:

There is a greater demand than supply for livers for use in orthologous liver transplantation (OLT) and less invasive procedure for the long term treatment of liver disease. Alternative treatments of liver disease with viral gene therapies have safety concerns. Exvivo and invivo nonviral methods of gene therapy have been shown to useful and have inherent advantages over each other. Delivery of naked DNA via electroporation and sonoporation has had some success but hydrodynamic delivery appears to be especially promising. Liposome and polymer vectors show generally lower levels of transfection but their improvement continues with the increased understanding of the mechanisms responsible for cell entrance, endosomal escape and nuclear envelope penetration. Transgene constructs such as Sleeping Beauty (SB) that integrate into the host genome have demonstrated good utility for persistent targeted expression while DNA repair constructs are disappointing and any future success likely depends on understanding the details of the mechanisms associated with DNA repair.