Transfecting of mouse embryonic stem cells with CRISPR/Cas9, sgRNA, and +/-donor template promotes HDR and enables development of efficient knockout or knock-in mouse models. CRISPR/Cas9 can also be used to develop inducible Cas9 mouse models to perform efficient somatic editing in vivo, with various organs as possible targets using either adenoassociated viruses (AAVs), lentivirus or nanoparticle mediated sgRNA delivery. Heckl et al. used CRISPR/Cas9 system via lentiviral delivery method to revive several inactivated oncogenes in primary hematopoietic stem and progenitor cells (HSPCs) to generate leukemia model. The targeted genes were: Tet2, Runx1, Dnmt3a, Nf1, Ezh2, and Smc3. CRISPR/Cas9 technology has also been adopted to develop organoid tumor models. For example, organoid models for colon cancer were constructed in vitro by using CRISPR to introduce mutations in tumor suppressor genes (APC, TP53, SMAD4, etc.) and modify oncogenes (KRAS, PI3K, etc.). Roper et al. established a protocol to induce site-directed tumors rapidly and efficiently in the distal colon of mice by utilizing colonoscopy-guided mucosal injection. This technique can be extrapolated to deliver viral vectors carrying Cre recombinase, CRISPR/Cas9 components, CRISPR-engineered mouse tumor organoids, or human cancer organoids to mice to model the adenoma-carcinoma-metastasis sequence of tumor progression.