Read the full study here:
rdcu.be/exqtH

Lastly, this wouldn't have been possible without a fantastic team of co-authors ☺️ Truly grateful to everyone who contributed and supported the work along the way.

#BaseEditing #PrecisionOncology #TP53 #CRISPR

TL;DR:
✅ Base editing can reverse oncogenic phenotypes
✅ Repairing TP53 hotspots restores a conserved p53 regulatory network
✅ Our platform is applicable to other mutations
✅ Precision editing + transcriptomics = powerful combo

Next up:
🏥 Patient-derived organoids
🧬 Multi-omics profiling
🧫 Single cells profiling

Our platform opens the door to a deeper, mutation-level understanding of cancer dependencies and vulnerabilities.

Why does this matter?
It’s a step toward precision oncology grounded in functional genetics - not just correlational genomics.

We now have a way to test which mutations matter and how they reshape cellular programs.

By combining base editing with transcriptomic profiling, we established a scalable framework to:

🧬 Correct mutations
📊 Measure downstream gene expression
💡 Reveal functional consequences
All in endogenous contexts.

🧫 Our platform can be extended to other cancer driver mutations

Repairing mutations in KRAS, PTEN or SMAD4, we found gene-specific differences in how mutations drive cancer cell fitness

Reinstating brakes (TP53) seems more effective than releasing a pedal stuck on gas (KRAS)

These effects were:
✔️ Consistent across tissue types
✔️ Independent of co-occurring mutations
✔️ Uniform across TP53 mutations (R273H vs R175H)

That suggests a conserved, mutation-independent p53 regulatory network that controls cancer cells. 🧬🛡️

🔬 What did we find?

🎯 Cancer cells are dependent on the mutant TP53 allele for survival.

When we corrected these mutations, we saw:
✅ Loss of oncogenic proliferation
✅ Reactivation of tumor suppressive transcriptional programs

Using adenine base editing (ABE), we precisely corrected TP53 hotspot mutations in a range of human cancer cell lines from different tissues.

No overexpression. No exogenous DNA. Just editing the native genome.