Researchers have developed a new genome-editing tool designed to target pancreatic ductal adenocarcinoma (PDAC), one of the deadliest cancers. The team engineered an improved cytosine base editor using a human protein called APOBEC3F. By combining artificial intelligence–based protein modeling with structure-guided engineering, they created optimized versions that improve editing efficiency and accuracy while reducing unwanted DNA changes.
The new editing system was designed to silence two major cancer-driving genes in pancreatic cancer, KRAS and MYC, which have long been considered difficult to target with traditional drugs. Instead of cutting DNA, the tool changes specific DNA letters to introduce stop signals in these genes, preventing the production of proteins that drive tumor growth. Researchers found that editing both genes at the same time produced stronger anti-cancer effects than targeting either gene alone.
The system was delivered using a dual adeno-associated virus platform and tested in cancer cell lines, patient-derived organoids, and mouse models. The treatment stopped cancer cell growth, reduced tumor size in mice, and extended survival. The new editor also showed improved precision and fewer unintended RNA edits compared with earlier genome-editing systems, suggesting it could offer a safer approach for future genetic therapies in pancreatic cancer.