Crispr Cas9 fluorine-containing PEI nanomedicine inhibits the growth of hepatocellular carcinoma cells by knocking out NEDD8-E2 conjugase UBC12 (UBE2M)

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Abstract

Knocking out the oncogene UBC12 with Crispr Cas9 can inhibit the Neddylation pathway and lead to excellent anticancer effect. However, how to deliver Crispr Cas9 into tumor cells is an urgent scientific problem. Based on the application of polyethyleneimine and its derivative (GMP in vivo-jetPEI) in clinical trials, we constructed fluorine-containing PEI to deliver Crispr Cas9 plasmid. In order to reduce the off-target effect of Crispr Cas9 nanomedicine, the targeting molecule TLS11a aptamer was modified on the surface of genetic nanomedicine to improve the efficiency of initiative. The experimental results showed that the released plasmid of Crispr Cas9 inhibited Neddylation by knocking out UBC12, thus achieving the goal of inhibiting the growth of tumor cells. The design of this genetic nanomedicine provides a scientific basis for the construction of non-viral genetic nanomedicine.

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