Molecular Lysis of Synovial Lining Cells by In Vivo Herpes Simplex Virus-Thymidine Kinase Gene Transfer

Abstract

Overview summary Previous studies have shown that synovial lining cells are susceptible to in vivo transfection using purified expression plasmid DNA. Roessler et al. now report on the use of a plasmid that mediates transient overexpression of herpes simplex virus thymidine kinase to transfect synovial lining cells in an animal model of proliferative inflammatory arthritis. After in vivo intraarticular transfection using the pNGVL-TK expression plasmid, the animals were treated with intravenous ganciclovir for a period of 3 days. They report that examination of the synovial tissues 21 days after completion of the gene therapy showed evidence of cytolysis that was confined to the synovial lining cells within inflamed synovium. No evidence of cytolysis or necrosis was observed in articular cartilage present within the treated joints. Similar methods to achieve a molecular lysis of the synovial lining layer may have applicability to the treatment of human inflammatory arthritis.