iduronate 2-sulfatase lentiviral gene therapy

Iduronate 2-sulfatase lentiviral gene therapy (AVR-RD-05) is an investigational autologous hematopoietic stem cell gene therapy (HSCGT) developed for the treatment of neuronopathic mucopolysaccharidosis type II (nMPS II, Hunter syndrome). The therapy involves ex vivo transduction of patient-derived CD34+ hematopoietic stem cells with a lentiviral vector encoding human iduronate 2-sulfatase (IDS) fused to a proprietary blood-brain barrier-targeting peptide, ApoEII, under the control of a myeloid-specific CD11b promoter. Once re-infused, these gene-modified cells engraft in the bone marrow and differentiate into myeloid cells (such as macrophages) that traffic to various tissues, including the brain. These cells produce and secrete supraphysiological levels of the functional IDS-ApoEII enzyme, which is taken up by neighboring cells via receptor-mediated transcytosis, thereby reducing the systemic and neurodegenerative accumulation of glycosaminoglycans (GAGs) like heparan sulfate and dermatan sulfate.

Other names

IDS-ApoEII lentiviral gene therapyLV-IDS-ApoEIILV.IDS.ApoEIIautologous CD34+ hematopoietic stem cells transduced ex vivo with CD11B lentiviral vector encoding human IDS tagged with ApoEIIiduronate 2-sulfatase lentiviral gene therapyiduronate2-sulfatase lentiviral gene therapyiduronate-2-sulfatase lentiviral gene therapy