Method of treating lysosomal storage diseases using nucleases and a transgene
First Claim
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1. A method for expressing and secreting exogenous glucocerbrosidase (GBA), α
- -galactosidase A (GLA), iduronate sulftase (IDS), or iduronidase (IDUA) protein in a liver cell in a mouse or human with a deficient GLA, GBA, IDS, or IDUA gene, the method comprising;
(i) intravenously injecting one or more adeno-associated viral (AAV) vectors encoding a pair of nucleases into the mouse or human, wherein the nucleases cleave an endogenous albumin gene in the liver cell; and
(ii) intravenously injecting an AAV vector comprising a donor sequence comprising a transgene encoding;
(a) an exogenous GBA protein into the mouse or human with the deficient GBA gene;
(b) an exogenous GLA protein into the mouse or human with the deficient GLA gene;
(c) an exogenous IDS protein into the mouse or human with the deficient IDS gene;
or(d) an exogenous IDUA protein into the mouse or human with the deficient IDUA gene, andwherein the transgene is flanked by sequences having homology with the endogenous albumin gene,such that the transgene is integrated into the endogenous albumin gene in the liver cell, 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 treatment and/or prevention of a lysosomal storage disease.
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3 Claims
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1. A method for expressing and secreting exogenous glucocerbrosidase (GBA), α
- -galactosidase A (GLA), iduronate sulftase (IDS), or iduronidase (IDUA) protein in a liver cell in a mouse or human with a deficient GLA, GBA, IDS, or IDUA gene, the method comprising;
(i) intravenously injecting one or more adeno-associated viral (AAV) vectors encoding a pair of nucleases into the mouse or human, wherein the nucleases cleave an endogenous albumin gene in the liver cell; and (ii) intravenously injecting an AAV vector comprising a donor sequence comprising a transgene encoding; (a) an exogenous GBA protein into the mouse or human with the deficient GBA gene; (b) an exogenous GLA protein into the mouse or human with the deficient GLA gene; (c) an exogenous IDS protein into the mouse or human with the deficient IDS gene;
or(d) an exogenous IDUA protein into the mouse or human with the deficient IDUA gene, and wherein the transgene is flanked by sequences having homology with the endogenous albumin gene, such that the transgene is integrated into the endogenous albumin gene in the liver cell, and the liver cell expresses and secretes the exogenous GBA, GLA, IDS, or IDUA protein. - View Dependent Claims (2, 3)
- -galactosidase A (GLA), iduronate sulftase (IDS), or iduronidase (IDUA) protein in a liver cell in a mouse or human with a deficient GLA, GBA, IDS, or IDUA gene, the method comprising;
Specification