While several glomerular diseases such as membranous nephropathy and anti-GBM disease are caused by autoantibodies, antigen-specific therapies are still missing. However, the involved autoantigens represent promising targets for treatments aiming at the underlying disease pathomechanisms while not affecting protective immunity. In the last funding period, we successfully generated antigen-specific autoimmune mouse models as well as therapeutic antibodies targeting pathogenic plasma cells. Based on this work, we now aim to develop and evaluate strategies to treat antibody-mediated diseases of the kidney – particularly membranous nephropathy and anti-GBM disease – on multiple new levels: 1.) Blocking of autoantibody binding to kidney autoantigens using target-specific nanobodies generated e.g. in a llama IgH transgenic mouse line. 2.) Engineering of heavy chain antibodies containing antigen extracellular domains for the specific elimination of antigen-specific autoantibodies (through Fc-receptor-mediated uptake and degradation of immune complexes) and autoantibody-producing B cells (through their specific B cell receptors). 3.) Gene delivery and knockdown using adeno-associated viral vectors (AAVs) displaying nanobodies against cell-specific surface molecules to control local disease processes. In summary, these studies will pave the way for novel antigen-specific treatments for glomerulonephritis, which may also be applicable to other inflammatory and autoantibody-mediated diseases.