Compositions and methods for modifying regulatory t cells
AssigneeThe Regents of the University of California
InventorsAlexander Marson, Jessica T. Cortez, Jeffrey A. Bluestone, Eric Shifrut, Frederic Van Gool
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Abstract
Provided herein are compositions and methods for modifying regulatory T cells. The inventors have identified nuclear factors that influence expression of Foxp3, a key transcriptional regulator of Treg cells. Treg cells can be modified by inhibiting and/or overexpressing one or more of these nuclear factors to produce stabilized Treg cells or destabilized Treg cells.
Claims35
A method of increasing human regulatory T (Treg) cell stability, the method comprising:
- inhibiting expression of one or more nuclear factors set forth in Table 1 and/or overexpressing one or more nuclear factors set forth in Table 2, in the human Treg cell.
A method of decreasing human Treg cell stability, the method comprising:
- inhibiting expression of a one or more nuclear factors set forth in Table 2 and/or overexpressing one or more nuclear factors set forth in Table 1, in the humanTreg cell.
A Treg cell comprising:
- (a) a genetic modification or heterologous polynucleotide that inhibits expression of a nuclear factor set forth in Table 1 and/or a heterologous polynucleotide that encodes a nuclear factor set forth in Table 2;
- (b) a genetic modification or heterologous polynucleotide that inhibits expression of a nuclear factor set forth in Table 2 and/or a heterologous polynucleotide that encodes a nuclear factor set forth in Table 1;
- or
- (c) at least one guide RNA (gRNA) comprising a sequence selected from Table 3.
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A method of destabilizing Tregs in a subject in need thereof, comprising inhibiting expression of a one or more nuclear factors set forth in Table 2 and/or overexpressing one or more nuclear factors set forth in Table 1, in the humanTreg cells of the subject.
A method of stabilizing Tregs in a subject in need thereof, comprising inhibiting expression of a one or more nuclear factors set forth in Table 1 and/or overexpressing one or more nuclear factors set forth in Table 2, in the humanTreg cells of the subject.
Dependencies are inferred from the claim text.