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US 2020/0368279 A1Published application
Controlled Transgene Expression in Regulatory T Cells
AssigneeSangamo Therapeutics, Inc.
InventorAnthony Conway
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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.
Claims20
A genetically engineered mammalian cell comprising a heterologous sequence in a FOXP3 locus in the genome, wherein
- the heterologous sequence comprises a transgene, wherein the transgene is under the transcriptional control of a FOXP3 promoter in the FOXP3 locus;
- and
- when the promoter is activated, the cell expresses both FOXP3 and a product of the transgene from the locus.
A method of making a genetically engineered mammalian cell, comprising:
- contacting a mammalian cell with a nucleic acid construct comprising (i) a heterologous sequence and (ii) a first homologous region (HR) and a second HR flanking the heterologous sequence flanking the heterologous sequence, wherein
- the heterologous sequence comprises a transgene,
- the first and second HRs are homologous to a first genomic region (GR) and a second GR, respectively, in a FOXP3 locus in the mammalian cell;
- and
- culturing the cell under conditions that allow integration of the heterologous sequence between the first and second GRs in the FOXP3 locus.
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Dependencies are inferred from the claim text.