PGK.TCIRG1 lentiviral vector

PGK.TCIRG1 lentiviral vector is a gene therapy vector designed to treat autosomal recessive osteopetrosis (ARO), a rare genetic disorder characterized by defective osteoclast function leading to increased bone density and severe bone phenotype. The vector uses a lentivirus to deliver the human TCIRG1 gene, which encodes a subunit of the vacuolar ATPase proton pump essential for osteoclast-mediated bone resorption. The TCIRG1 gene is expressed under the control of the phosphoglycerate kinase (PGK) promoter in this construct. This therapy aims to restore functional osteoclasts by transducing hematopoietic stem and progenitor cells (HSPCs), thereby correcting the disease phenotype. Preclinical studies in murine models have demonstrated improved survival and correction of bone abnormalities after treatment with this lentiviral vector. A phase I clinical trial was initiated but discontinued due to unrelated early patient death[1][2].