CRISPR-Cas9 Fluorine-Containing PEI Nanomedicine Inhibits the Growth of Hepatocellular Carcinoma Cells by Knocking Out NEDD8-E2 Conjugase UBC12 (UBE2M)

Knocking out the oncogene UBC12 using CRISPR-Cas9 inhibited the neddylation pathway and produced significant anticancer effects. However, the delivery of CRISPR-Cas9 into tumor cells remains an urgent scientific challenge. Based on the clinical applications of polyethyleneimine (PEI) and its derivatives (GMP in vivo -jetPEI), we constructed a fluorinecontaining PEI to deliver CRISPR-Cas9 plasmids. To reduce off-target effects and improve delivery efficiency, we modified the nanomedicine surface with TLS11a aptamer-targeting molecules. Under the guidance of these targeting molecules, the CRISPR-Cas9 plasmid is internalized by liver cancer cells where it knocks out the UBC12 oncogene, inhibits the ned-dylation pathway in hepatocellular carcinoma cells, and induces the accumulation of cullin-ring ligases tumor-suppressor substrates, thereby suppressing liver cancer growth. This genetic nanomedicine design provides a scientific basis for the development of non-viral genetic nanomedicines.