HLA Class II Deficient Cells, HLA Class I Deficient Cells Capable of Expressing HLA Class II Proteins, and Uses Thereof

Abstract

The invention provides isolated primate cells preferably human cells that comprise a genetically engineered disruption in a human leukocyte antigen (HLA) class II-related gene, which results in deficiency in MHC class II expression and function. This invention also provides isolated cells further comprising a genetically engineered disruption in a beta-2 microglobulin (B2M) gene, which results in HLA class I / class II deficiency. Also provided are the method of using the cells for transplantation and treating a disease condition.

Description

CROSS REFERENCE[0001]This application claims priority to U.S. provisional patent application Ser. No. 61 / 625,314 filed Apr. 17, 2012, incorporated by reference herein in its entirety.STATEMENT OF GOVERNMENT RIGHTS[0002]This invention was made with government support under grant numbers R01GM086497 and R01DK55759 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Human pluripotent stem cells have the potential to treat diseases affecting almost every organ system. However, the clinical use of human pluripotent stem cells and their derivatives has a major limitation—rejection of transplanted cells by the recipient due to differences in the major histocompatibility complex.[0004]The major histocompatibility complex (MHC) is a cell surface multi-component molecule found in all vertebrates that mediates interactions of leukocytes with other leukocytes or other cells. The MHC gene family is divided into three g...

AI Technical Summary

Benefits of technology

The present invention provides isolated cells that have a genetically engineered disruption in a human leukocyte antigen (HLA) class II-related gene, such as regulatory factor X-associated ankyrin-containing protein (RFXANK), regulatory factor X5 (RFX5), regulatory factor XAP (class II transactivator (CIITA), HLA-DPA (α chain), HLA-DQB, HLA-DRB, HLA-DRA, HLA-DRA, HLA-DOA, HLA-DOB, and HLA-DMB. The cells can also express one or more immunomodulatory genes, such as a polynucleotide capable of encoding an HLA class II protein or a single chain fusion HLA class I protein. The cells can be primate cells, such as stem cells, and can be used for immunotherapy and gene therapy applications.

Problems solved by technology

However, the clinical use of human pluripotent stem cells and their derivatives has a major limitation—rejection of transplanted cells by the recipient due to differences in the major histocompatibility complex.

This time-consuming, technically difficult, and expensive process is a major factor preventing stem cell-based therapies from entering clinical trials.

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