Huge thanks to my PI Georg Seelig, Chris Yin, our collaborators at the Altius Institute @meuleman.bsky.social and Seattle Children’s Research Institute, and to the NIH for support.

📢 Also, catch my talk Friday 2PM in the “Theory & Practice of Synthetic Biology” session at BMES!

🗺️ Finally, we built an atlas of ~52k enhancers targeting 261 cell types & states! These are ready to use (no model running needed!). See the paper’s SI.

We highlight a set of enhancers designed to target intermediate states during stem cell differentiation to cardiomyocytes.

🔍Using explainable AI, we found that combinations of Transcription Factor Binding Sites (TFBSs) drive function in many enhancers. We also identified TFBSs whose effects on accessibility vs. activity diverged, explaining some design failures.

✅ We experimentally validated enhancers in 10 human cell lines (functional in 9!) + mouse retina
📈 Designs matched expected specificity & outperformed natural genomic controls
⚙️ We demonstrated enhancers with tunable activity & multi-cell-type targeting

These enhancers should enable programming synthetic DNA with cell- or tissue-specific gene expression, with broad applications in gene therapy, regenerative medicine, and synthetic biology.