Adeno associated viral vector gene therapy for treatment of autoimmune kidney disease

Autoimmune kidney diseases, particularly lupus nephritis and ANCA associated vasculitis are associated with low expression of DNase I a critical enzyme for degrading Extracellular DNA released from pro inflammatory cell death. Administration of exogenous DNase I can therapeutically treat ANCA associated vasculitis in animal models- however it has a short half life and requires twice daily treatment intravenously a cumbersome form of treatment for patients. However using gene therapy targeting the liver we can use one shot of an adeno associated viral vector that enable hepatocytes from the liver to release super physiological amounts of DNase I overcoming the short half life. This project will capitalise on our preliminary data and now characterise this therapeutic effect to translate these pre clinical findings into the clinic. Aim 1: Demonstrate that adeno associated viral vector delivery of DNase I is therapeutic in acute kidney injury (replicating first onset) Aim 2: Demonstrate that adeno associated viral vector delivery of DNase I is therapeutic in the maintenance phase of ANCA associated vasculitis Aim 3: Demonstrate safety and efficacy in animal models of infection to demonstrate that Adeno associated viral vector DNase I is superior in providing treatment compared to standard of care in relation to rendering the host immunocomrpomised.