Rationally and in silico guided APOBEC3F-directed CBE for enhanced PDAC genetic therapy - PubMed
4 days ago
- #Gene Editing
- #CRISPR
- #Oncology
- Cytosine base editors (CBEs) enable precise C-to-T conversion with therapeutic potential in oncology.
- Evolutionary scale modeling (ESM) and structure-guided mutagenesis were used to remodel human APOBEC3F (A3F), creating high-performance CBEs.
- A3F-CBEs show 1.9- and 3.3-fold higher on-target editing efficiency compared to A3A- and Anc689-BE4max.
- High-accuracy A3F-CBEs improve editing specificity by up to 3.0-fold over haA3A-G.
- A dual-AAV platform with A3F-BE4max and dual gRNAs targets KRAS and MYC in pancreatic ductal adenocarcinoma (PDAC) models.
- The platform silences oncogenes, inhibits PDAC cell proliferation in vitro and in patient-derived organoids (PDOs), and suppresses tumor growth in mice.
- ESM-guided A3F-based CBEs offer a precise platform for cancer genetic therapy.