Immensely grateful to the @SynRegLab for this work!
Congratulations to all authors!

Notably, PAK1 was upregulated EXCLUSIVELY in FGFR-negative patient tumors, and PAK1 inhibitors re-sensitized human + mouse metastatic SCC cells to anti-FGFR therapy; a strong therapeutic synergy.

Most importantly, RESTRICT-seq UNIQUELY flagged PAK1 as a key resistance driver — completely invisible by standard CRISPR screens, buried under the noise of non-specific gene dropouts.

This is the power of #PrecisionGenomics: drug-synergistic vulnerabilities clearly revealed.

When compared to conventional wtCas9 screens, the difference was striking!
RESTRICT-seq reduced clonal drift, ensuring gRNA counts reflect true biology; less artifacts!

To achieve this we engineered arCas9-SPARK, a live-cell biosensor that lets us track Cas9 movements in and out of the nucleus in real-time.
It's fast⚡️: In and Out within 15 min!