Liver-targeted gene and cell therapies: An overview

Abstract

Until very recently, management of several liver malignancies, viral hepatitis, hepatic cirrhosis, and hereditary metabolic diseases remained unsatisfactory, and thus, effi cient therapeutic approaches have always been in need. In parallel with recent advances in molecular biology and recombinant DNA technologies, research in liver diseases and the quest for molecular insights of disease pathology have witnessed remarkable progression, and early and specifi c detection of genetic, infectious, and malignant liver diseases has become feasible like never before. Several molecular approaches combining genetics, biology, chemistry, and computer sciences have been introduced, and in particular, gene- and cell-based therapies opened up new opportunities that step out beyond classical pharmacology. Gene therapy emerged as promising therapeutic strategy aiming to introduce genetic material into cells to generate curative effects. Gene therapy comprises various methods of gene delivery and innovative overexpression and silencing designs for specifi c therapeutic needs (Kay MA, Nat Rev Genet 12:316-328, 2011). Cell-based therapies, on the other hand, aim to use biologically active iving cells instead of DNA or RNA as treatment modality. Several extracorporeal and implantable cell therapies have been developed, such as bioartifi cial liver (Baquerizo A, Mhoyan A, Kearns-Jonker M, Arnaout WS, Shackleton C, Busuttil RW et al, Transplantation 67:5-18, 1999) for short-term treatment and liver cell transplantation for permanent liver replacement (Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI et al, N Engl J Med 338:1422-1426, 1998). In this chapter, we will briefl y discuss the current theories and potential applications of gene- and cellbased therapies for the treatment and/or prevention of various liver diseases.