Genetically Modified Hepatocyte Populations

The method of any of the preceding claims, wherein the at least one NK cell decoy receptor comprises CD47, a B2M-HLA-E fusion, or a combination thereof.

A method of treating a subject for a condition, the method comprising:

• administering to the subject an effective amount of hypoimmunogenic hepatocytes or progenitors, wherein the hypoimmunogenic hepatocytes or progenitors each comprise an HLA class I deficiency and a transgene encoding at least one NK cell decoy receptor, optionally wherein the condition is a liver condition.

A non-human mammal comprising an engrafted cell population, the cell population comprising a plurality of hypoimmunogenic human hepatocytes or progenitors thereof, wherein each hepatocyte or progenitor of the plurality comprises an HLA class I deficiency and a transgene encoding at least one NK cell decoy receptor, optionally wherein the HLA class I deficiency comprises a B2M deficiency and the at least one NK cell decoy receptor comprises CD47, a B2M-HLA-E fusion, or a combination thereof.

A cell population comprising a plurality of hypoimmunogenic primary human hepatocytes, wherein each hepatocyte of the plurality comprises an HLA class I deficiency and a transgene encoding at least one NK cell decoy receptor, optionally wherein the HLA class I deficiency comprises a B2M deficiency and the at least one NK cell decoy receptor comprises CD47, a B2M-HLA-E fusion, or a combination thereof.

A method of generating genetically modified human hepatocytes, the method comprising:

• contacting a cell population comprising human hepatocytes or progenitors thereof with an integrating vector comprising a transgene encoding a gene product under conditions sufficient for functional integration of the transgene to produce genetically modified hepatocytes or progenitors thereof comprising the integrated transgene;
• and
• transplanting the genetically modified hepatocytes or progenitors thereof into an in vivo bioreactor and maintaining the in vivo bioreactor under conditions sufficient for expansion of the genetically modified hepatocytes or progenitors to generate an expanded population of genetically modified human hepatocytes that express the gene product, optionally wherein the in vivo bioreactor is a mouse, rat, or pig.

A non-human mammal comprising an engrafted cell population, the cell population comprising a plurality of genetically modified human hepatocytes, wherein each hepatocyte of the plurality comprises a functionally integrated transgene encoding a gene product.

A cell population comprising a plurality of hypoimmunogenic primary human hepatocytes, wherein each hepatocyte of the plurality comprises an HLA class I deficiency and a transgene encoding at least one NK cell decoy receptor.