Beha, Marcel Janis; Kim, Joo-Chan; Im, San Hae; Kim, Yunsu; Yang, Seungju; Lee, Juhee; Nam, Yu Ri; Lee, Haeshin; Park, Hee-Sung; Chung, Hyun Jung

DOI: PMID:

Abstract

Bioconjugation of proteins can substantially expand the opportunities in biopharmaceutical development, however, applications are limited for the gene editing machinery despite its tremendous therapeutic potential. Here, a self-delivered nanomedicine platform based on bioorthogonal CRISPR/Cas9 conjugates, which can be armed with a chemotherapeutic drug for combinatorial therapy is introduced. It is demonstrated that multi-functionalized Cas9 with a drug and polymer can form self-condensed nanocomplexes, and induce significant gene editing upon delivery while avoiding the use of a conventional carrier formulation. It is shown that the nanomedicine platform can be applied for combinatorial therapy by incorporating the anti-cancer drug olaparib and targeting the RAD52 gene, leading to significant anti-tumor effects in BRCA-mutant cancer. The current development provides a versatile nanomedicine platform for combination treatment of human diseases such as cancer.

Keywords

bioorthogonal ; cancer therapy ; chemotherapeutic drugs ; combinatorial delivery ; CRISPR ; Cas9 ; gene editing ; nanomedicines ; unnatural amino acids

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