Fig. 4

Introduction of mutant Kras variants into pancreatic cells using AAV/Cas9-mediated HDR drives the formation of metastatic PDAC. a Schematic of retrograde pancreatic ductal injection of AAV-Kras ^HDR/sgKras/Cre (∼1.7 × 10¹¹ vector genomes per mouse) into PT;H11 ^LSL-Cas9 mice to induce pancreatic cancer. b Histology of pancreatic tumors initiated by retrograde pancreatic ductal injection of AAV-Kras ^HDR/sgKras/Cre into PT;H11 ^LSL-Cas9 mice. Scale bars = 75 µm. c Histology of metastases in the lymph node (upper panel) and diaphragm (lower panel) in PT;H11 ^LSL-Cas9 mice with PDAC. Scale bars = 50 µm. d Incidence of PDAC, DTCs in the peritoneal cavity, and metastases in the indicated genotypes of mice (shown as the number of mice with cancer, DTCs, or metastases out of the total number of mice analyzed), 3–13 months after transduction with either AAV-Kras ^HDR/sgKras/Cre or AAV-Kras ^HDR/Cre (∼2.9 × 10¹¹ vector genomes per mouse). AAV-Kras ^HDR/sgKras/Cre was administered at the stock concentration (“undil.”) or at a 1:10 dilution (“1:10”). e HDR-generated oncogenic Kras alleles in individually dissected pancreatic tumor masses. Number of tumors with each allele is indicated. Alleles that were not identified in any pancreatic tumor masses are not shown