PRJNA714135
Clinically-driven design of synthetic gene regulatory programs in human cells
In this study, we designed human genome-orthogonal synthetic regulators called "synZiFTRs" (synthetic Zinc Finger Transcription Factors). To evaluate the impact of our synthetic regulators on native regulation, we performed RNA-sequencing analysis on HEK293FT cell lines expressing three representative synZiFTRs (ZF1, ZF3, ZF10) and benchmarked these against a TetR-based activator. SynZiFTR regulation profiles are highly specific, minimally affecting native transcript profiles and importantly compare favorably with that of TetR. These results establish a collection of compact, human-based, and genome-orthogonal synZiFTRs optimized for artificial gene expression control in human cells.