| 초록 |
Cancer gene therapy based on the clustered regularly interspaced short palindromic repeats (CRISPR) system has been challenging due to the poor delivery and efficacy in vivo. Herein, we report the development of nano-assembled ribonucleoprotein complexes (NanoRNP), which can efficiently block the PD-L1 immune checkpoint and induce anti-tumor effect in vivo. We utilize CRISPR-associated protein 9 (Cas9) that is chemically derivatized with branched polyethyleneimine, which condenses with single-guide RNA and modified DNA to form stabilized NanoRNP. In vivo delivery in a mouse melanoma demonstrates that NanoRNP can induce indels in tumor at high frequencies resulting in suppression of tumor growth. Blockade of the PD-L1 checkpoint by NanoRNP in tumor promotes T cell infiltration and effector cytokine release, as well as inhibition of immune-suppressive myeloid cells. The current system suggests a promising strategy as a in vivo gene editing platform for cancer immunotherapy. |
