autologous hepatocytes transduced with low-density lipoprotein receptor gene

Autologous hepatocytes transduced with the low-density lipoprotein receptor (LDLR) gene is a pioneering ex vivo gene and cell therapy developed primarily for the treatment of Homozygous Familial Hypercholesterolemia (HoFH). The procedure involves a partial hepatectomy to harvest the patient's own liver cells, followed by the isolation and cultivation of hepatocytes. These cells are then transduced using a recombinant retroviral vector (typically based on the Moloney murine leukemia virus) carrying a functional human LDLR cDNA. The genetically modified hepatocytes, now expressing functional LDL receptors, are re-infused into the patient's liver via a catheter in the portal vein. Once engrafted, these cells are intended to clear low-density lipoprotein cholesterol from the systemic circulation, a function missing in HoFH patients. Although this approach demonstrated safety and proof-of-concept in clinical trials during the early 1990s, it was eventually discontinued because the level of LDLR expression and the efficiency of cell engraftment were insufficient to achieve a durable and significant therapeutic reduction in plasma cholesterol levels.

Other names

ex vivo gene therapy for LDLRWilson's ex vivo hepatocyte gene therapyretrovirus-mediated gene transfer of LDLR