Controlled transgene expression in regulatory t cells
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Publication Number
US-12509703-B2
Publication Date
2025-12-30
Expiration Date
Abstract
The present disclosure provides mammalian cells such as regulatory T cells containing a transgene in the FOXP3 genomic locus. Also provided are methods of generating the cells and methods of using the cells to treat patients in need of immunosuppression.
Core Innovation
The claimed genetically engineered, isolated mammalian cell comprises a heterologous sequence integrated in intron 4, 9, or 10 of a FOXP3 locus. The sequence includes downstream FOXP3 exon sequences, a transgene under transcriptional control of the endogenous FOXP3 promoter, and an upstream splice acceptor. This arrangement allows expression of both FOXP3 protein and a transgene product, while producing a full-length FOXP3 mRNA transcript.
The method claim covers making an engineered mammalian cell with a heterologous sequence configured for integration into the same site in intron 4, 9, or 10 of the FOXP3 locus. The content also describes regulatory T cells as a cell type and illustrates FOXP3-locus integration constructs. Because background and summary sections are absent, the problem being solved is not explicitly described in patent.
Claims Coverage
The claims identify two independent claims covering a genetically engineered mammalian cell and a method of making such a cell, comprising two inventive features.
FOXP3-locus cell expressing FOXP3 and a transgene
An isolated, genetically engineered mammalian cell has a heterologous sequence integrated in intron 4, 9, or 10 of a FOXP3 locus. The sequence comprises contiguous downstream FOXP3 exon sequences, a transgene under transcriptional control of the endogenous FOXP3 promoter, and an upstream splice acceptor, allowing transcription of a full-length FOXP3 mRNA transcript and expression of both FOXP3 protein and a transgene product.
Making a cell with a heterologous sequence integrated in the FOXP3 locus
The method covers making a genetically engineered mammalian cell with a heterologous sequence configured for integration into intron 4, 9, or 10 of a FOXP3 locus. The sequence architecture supports expression of FOXP3 protein and a transgene product under the control of the endogenous FOXP3 promoter and transcription of a full-length FOXP3 mRNA transcript. [procedural detail omitted for safety]
The two independent claims cover the engineered mammalian cell and a method of making it, each centered on FOXP3-locus integration configured to support expression of a transgene product alongside full-length FOXP3.
Stated Advantages
Not explicitly described in patent.
Documented Applications
The claims describe CAR or TCR transgene products specific for an autoantigen, a B cell antigen such as CD19 or CD20, or an allogeneic HLA class I molecule such as HLA-A2, with drawings illustrating an HLA-A2-specific CAR architecture.
The document identifies antigen-directed immunosuppression using regulatory T cells for autoimmune disease.
The document identifies antigen-directed immunosuppression using regulatory T cells in tissue transplantation.
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