HLA homozygous cells

• US 8,586,358 B2
• Filed: 12/21/2011
• Issued: 11/19/2013
• Est. Priority Date: 03/09/2007
• Status: Active Grant

• Current Assignee: University of Washington
• Original Assignee: University of Washington
• Inventors: Russell, David W., Hirata, Roli K.
• Primary Examiner(s): Crouch, Deborah
• Application Number:
  US13/333,010
• Publication Number:
  US 20120093790A1
• Time in Patent Office: 699 Days
• Field of Search: None
• US Class Current: 435/366
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/34 Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes vascular smooth muscle A61K35/44
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: C07K 14/70539 MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C12N 15/907 in mammalian cells
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2750/14151 Methods of production or purification of viral material
• CPC Class Codes: C12N 5/0606 Pluripotent embryonic cells, e.g. embryonic stem cells [ES] embryonic germ cells C12N5/0611, induced pluripotent stem cells C12N5/0696

Abstract

The present invention provides methods of generating a mammalian cell that is homozygous at a locus of interest, as well as cells made by the method. The present invention further provides methods of using the cells.

Claims

1. An isolated human stem cell or a progeny thereof, wherein the stem cell or progeny thereof is homozygous for a human leukocyte antigen (HLA) haplotype, the HLA haplotype comprising an entire HLA locus;

and wherein at least about 90% of the non-HLA loci in the cell or progeny thereof are heterozygous and the cell is not a parthenogenic stem cell.

2. The isolated human stem cell or progeny thereof of claim 1, wherein said cell is selected from an embryonic stem cell, a neural stem cell, a mesenchymal stem cell, a hematopoietic stem cell, and a differentiated cell.

3. The isolated human stem cell or progeny thereof of claim 1, wherein the HLA haplotype comprises alleles found in a common HLA haplotype present in a selected human population.

4. A differentiated progeny cell of the isolated human stem cell of claim 1, wherein the cell is selected from a neural cell, a glial cell, a pancreatic islet cell, a cardiomyocyte, a mesenchymal lineage cell, and a hematopoietic stem cell lineage cell.

5. A composition comprising the isolated human stem cell or progeny thereof of claim 1.

6. A composition comprising the differentiated progeny cell of claim 4.

7. The composition of claim 6, wherein the differentiated progeny cell is associated with a matrix.

8. The composition of claim 6, wherein the differentiated progeny cell is present in a tissue sheet.

9. The isolated human stem cell or progeny thereof of claim 1, wherein the stem cell or progeny thereof is homozygous for all non-HLA loci present on the short-arm of chromosome 6 that are distal to both the chromosome'"'"'s centromere and said entire HLA locus.