Bioorthogonal CRISPR conjugates for in vivo gene editing and therapy
발표자
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초록
내용
Gene editing based on the CRISPR/Cas system has emerged as an innovative tool for therapy of human diseases. Here, we introduce a nanomedicine platform based on bioorthogonal CRISPR/Cas conjugates, which can be armed with a chemotherapeutic drug for combinatorial therapy, or functionalized with a targeting antibody for specific delivery. We developed a nanomedicine platform can be applied for combinatorial therapy by incorporating the anti-cancer drug olaparib and a carrier polymer, for in vivo delivery and combinatorial therapy of BRCA-mutant breast cancer. We could also achieve cell-specific delivery by conjugation of the CRISPR machinery with a HER2-targeted antibody, and demonstrated that anti-tumor efficacy in a HER2-positive ovarian cancer model in mice. We anticipate that this development can serve as a versatile therapeutic platform for the treatment of various cancers and genetic diseases.