Pancreatic infusion of the engineered AAV into adult mice leads to the expression of sgKras and Cre, which in turn drives the expression of Cas9, deletion of Trp53, and introduction of the engineered Kras variant into the Kras locus through homology-directed repair, ultimately facilitating the growth of PDA that is histologically indistinguishable from those derived from conventional KPC (KrasLSL-G12D;Trp53LSL-R172H or Trp53flox/flox;Pdx1-Cre) mice57. Here, KRAS is linked to Patent ductus arteriosus.