Animal models of reccurrent hepatocellular carcinoma and uses thereof

A recurrent hepatocellular carcinoma (HCC) model generating system comprising the following components:

• (i) a CRISPR-Cas expression vector comprising:
• a nucleic acid sequence encoding a CRISPR-associated (Cas) endonuclease;
• a nucleic acid sequence encoding a single guide RNA (sgRNA), wherein the sgRNA is designed to specifically target and bind to a predetermined sequence within a Tp53 gene of a target non-human animal;
• and
• a delivery vector carrier that facilitates the delivery and expression of the sequences encoding the Cas endonuclease and the sgRNA in target liver cells,
• wherein in the target liver cells of the target animal the combination of the Cas endonuclease and the sgRNA leads to inhibition of expression of the Tp53 gene in the target liver cells;
• (ii) a transposase expression vector comprising:
• a nucleic acid sequence encoding a transposase;
• and
• a first antibiotic resistance gene for the selection of cells containing the transposase expression vector,
• wherein the transposase expression vector is designed to lead to expression of the transposase in the target liver cells;
• and
• (iii) a transposon expression vector comprising:
• a nucleic acid sequence encoding an oncogene;
• a pair of inverted terminal repeat (ITR) sequences located on either side of the sequence encoding the oncogene, wherein the ITR sequences are recognized and bound by the transposase;
• and
• a second antibiotic resistance gene for the selection of cells containing the transposon expression vector,
• wherein the transposon expression vector is designed to lead to expression of the oncogene in the target liver cells.