HLA G-MODIFIED CELLS AND METHODS

摘要

Disclosed herein are genetically modified cells expressing HLA-G (e.g., cell surface HLA-G) persistently, and nucleic acid compositions useful for generating such genetically modified cells. Also disclosed are cell therapy methods that utilize genetically modified cells that express HLA-G persistently. The HLA-G genetic modifications described herein provide the cells with characteristics of reduced immunogenicity and/or improved immunosuppression, such that these cells have the promise of being universal or improved donor cells for transplants, cellular and tissue regeneration or reconstruction, and other therapies.

主权项

1. A genetically modified mammalian cell that has reduced immunogenicity and/or improved immunosuppression as compared to the mammalian cell without said genetic modification, wherein:
(i) the genetically modified mammalian cell comprises an exogenous nucleic acid comprising: (a) a nucleic acid sequence encoding an HLA-G protein having an amino acid sequence at least 95% identical to consensus wild-type human HLA-G, and comprising one or more amino acid mutations that reduce retention of HLA-G in the endoplasmic reticulum-golgi recycling pathway; and (b) a 3′ untranslated region (UTR) that is at least 85% identical to the 3′ untranslated region sequence of the consensus wild-type human HLA-G gene and does not comprise SEQ ID NO:4; and (ii) the encoded HLA-G protein is expressed by the genetically modified mammalian cell for at least seven weeks.