CisFalcon

AI now designs synthetic enhancers meant to switch a gene on in one cell type and stay silent everywhere else. When one fires in the wrong cell, the consequence can be clinical: in a real enhancer-AAV gene therapy for Dravet syndrome, driving the gene in all neurons instead of only interneurons raised mortality in mice, while the cell-type-specific version was safe and corrected seizures (Mich et al., Sci Transl Med 2025). CisFalcon catches that failure from sequence, before a lab spends six weeks and a synthesis run. Paste a designed enhancer into the live tool (https://cisfalcon-lifesci.fly.dev/) and it scores cell-type specificity against a frozen external measured-activity model, then applies the prescribed motif edit and re-scores from failing to passing (a proposed fix, not wet-lab validated). On 93,435 independent designs from a different lab it separates failures at AUROC 0.80; ranking a batch safest-first cuts wasted syntheses about 70%. We also tested the harder within-tissue question directly, on real in-vivo cortical enhancers with an independent model (AUROC 0.71). It flags risk; it does not design DNA.