Improvement of Bone and Dental Phenotype of Murine Hypophosphatasia Mediated by a Single Injection of Lentiviral Gene Therapy

Abstract

Background: Alkaline phosphatase has 4 isozymes, tissue non-specific alkaline phosphatase (TNAP), placental alkaline phosphatase (PLAP), intestinal alkaline phosphatase and germ-cell alkaline phosphatase. Hypophosphatasia (HPP) is an inherited skeletal disease caused by mutations of the gene encoding TNAP. Although TNAP is expressed in various tissues, the primary HPP symptoms appear in bones and teeth. The clinical severity of HPP varies widely from the most severe (perinatal, infantile and childhood) to the mildest forms (adult, and odonto-hypophosphatasia). We reported that gene therapy using a single injection of lentiviral vector expressing bone-targeted TNAP (TNAP-D 10 ) is effective in preventing all the skeletal of HPP in TNAP knockout (Alpl −/− ) mice as the model of infantile HPP. Objective: In this study we focus on evaluating the efficacy of treatment with gene therapy on the bone and teeth using TNAP-D 10 and also we investigate the feasibility of gene therapy using bone-targeted PLAP (PLAP-D 10 ). Methods and Findings: We used