Method of treating lysosomal storage diseases
First Claim
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1. A method for expressing and secreting exogenous glucocerebrosidase (GBA), α
- galactosidase (GLA), iduronate-2-sulfatase (IDS) or alpha-L iduronidase (IUDA) protein in a liver cell of a human or a mouse in need thereof, the method comprising;
(a) intravenously administering one or more AAV vectors encoding a pair of zinc finger nucleases that cleaves in intron 1 or 12 of an endogenous albumin gene into said human or mouse containing the liver cell and disrupts expression of the albumin gene; and
(b) intravenously administering an AAV vector comprising a donor sequence comprising a transgene encoding;
(i) an exogenous GBA protein;
(ii) an exogenous GLA protein;
(iii) an exogenous IDS protein;
or (iv) an exogenous IDUA protein, into the human or mouse liver cell of said human or mouse, wherein the transgene encoding the protein is flanked by regions of homology to intron 1 or 12 of the cleaved endogenous albumin gene, such that the transgene is integrated by homology directed repair into intron 1 or 12 of the cleaved endogenous albumin gene, and the liver cell expresses and secretes the exogenous GBA, GLA, IDS, or IDUA protein.
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Abstract
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 the provision of proteins lacking or deficient in subjects with a lysosomal storage disease and treatment and/or prevention of lysosomal storage diseases.
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Citations
4 Claims
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1. A method for expressing and secreting exogenous glucocerebrosidase (GBA), α
- galactosidase (GLA), iduronate-2-sulfatase (IDS) or alpha-L iduronidase (IUDA) protein in a liver cell of a human or a mouse in need thereof, the method comprising;
(a) intravenously administering one or more AAV vectors encoding a pair of zinc finger nucleases that cleaves in intron 1 or 12 of an endogenous albumin gene into said human or mouse containing the liver cell and disrupts expression of the albumin gene; and (b) intravenously administering an AAV vector comprising a donor sequence comprising a transgene encoding;
(i) an exogenous GBA protein;
(ii) an exogenous GLA protein;
(iii) an exogenous IDS protein;
or (iv) an exogenous IDUA protein, into the human or mouse liver cell of said human or mouse, wherein the transgene encoding the protein is flanked by regions of homology to intron 1 or 12 of the cleaved endogenous albumin gene, such that the transgene is integrated by homology directed repair into intron 1 or 12 of the cleaved endogenous albumin gene, and the liver cell expresses and secretes the exogenous GBA, GLA, IDS, or IDUA protein. - View Dependent Claims (2, 3, 4)
- galactosidase (GLA), iduronate-2-sulfatase (IDS) or alpha-L iduronidase (IUDA) protein in a liver cell of a human or a mouse in need thereof, the method comprising;
Specification