In vivo cell therapies require compact regulatory elements restricting transgene expression to target cells. We developed promoters driving strong expression in T and NK cells while remaining silent in HSCs and B cells, enabling on-target activity for in vivo CAR therapy. Arrayed libraries of native elements were built from ATAC-seq and RNA-seq datasets; a pooled 36,000-member synthetic library was built from combinatorial TFBS motifs. Both were screened in primary human HSCs, B, NK, and T cells (n=3 donors). Native elements were strong but nonspecific; synthetic hits were specific but weak. Combining both yielded optimized promoters.