Method of treating mucopolysaccharidosis type I or II
Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of a lysosomal storage disease.
1. A method of treating a mouse or human with mucopolysaccharidosis type I (MPS I) or mucopolysaccharidosis type II (MPS II) disease, the method comprising
intravenously injecting first and second AAV vectors, encoding first and second ZFNs of a pair of zinc finger nucleases that cleave in an endogenous albumin gene, into the mouse or human with MPS I or MPS II disease;
intravenously injecting a third AAV vector comprising a transgene encoding (a) an iduronidase (IDUA) protein into the mouse or human with MPS I disease or (b) a DNA sequence encoding an iduronate sulfatase (IDS) protein into the mouse or human with MPS II disease, wherein the transgene is flanked by sequences having homology with the endogenous albumin gene;
wherein the first, second and third AAV vectors are delivered at a ratio of 1:1:8 and further wherein the transgene is integrated into the endogenous albumin gene in liver cells of the mouse or human and the liver cells express and secrete therapeutic amounts of the IDUA or IDS protein and a symptom of the MPS I or MPS II disease is treated in the mouse or human.
2. The method of claim 1 , wherein the method treats neurological deficits associated with MPS I or MPS II disease.
3. The method of claim 1 , wherein the method reduces GAG accumulation in the mouse or human.
4. The method of claim 1 , wherein the AAV vectors are AAV2 and/or AAV6 vectors.