Using gene editing to add a viral gene that helps make stem cells less likely to trigger immune reactions

US2 expression selectively reduces HLA-A2 surface levels while maintaining total HLA-I at low levels.

• Mismatches in HLA haplotypes can lead to increased risk of graft failure due to immune rejection.
• Current methods to eliminate HLA class I surface expression, such as beta-2 microglobulin knockout, may trigger adverse immune responses.
• Introducing a cytomegalovirus-derived US2 sequence allows for selective reduction of HLA-A2 without complete HLA-I ablation.
• Flow cytometry results indicate that US2 reduces HLA-A2 surface expression while preserving low total HLA-I levels.
• Coculture assays demonstrate that US2 expression prevents activation of HLA-A2 alloreactive T-cells without enhancing natural killer cell activity.

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