Therefore, we developed a tumor suppressor/oncogene ultra-deep sequencing pipeline to determine whether editing and short-term ex vivo expansion leads to disruption and/or enrichment of cancer-associated variants when delivered in a clinically relevant context—i.e., when high-fidelity Cas914 is transiently delivered as RNP via electroporation to human primary HSPCs without subpopulations of cells with pre-existing tumorigenic variants. The gene discussed is RNPC3; the disease is cancer.