CRISPR/Cas9-based genome editing for multimodal synergistic cancer nanotherapy

The revolutionary clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) gene editing technology offers unprecedented opportunities for curing cancer. As a flexible and powerful gene editing tool, it has been broadly used for precise manipulation of single or multiple cancer-related targets in vitro and in vivo. By partnering gene therapy with other therapeutic modalities, this intervention at the genetic level can be readily leveraged to achieve optimal curative effects against cancer, laying a solid foundation for the development of CRISPR/Cas9-based synergistic cancer therapy. Here, we provide a comprehensive overview of recent advances in this nanomedicine-enabled/augmented advanced multimodal cancer therapy based on the CRISPR/Cas9 system, involving gene-chemotherapy, gene-photothermal therapy, gene-photodynamic therapy, gene-sonodynamic therapy, and gene-immunotherapy, and discuss their cooperative mechanisms in detail. We also highlight the advantages and limitations of these collaborative anticancer strategies and outlook on their potential challenges in future clinical translation. It is reasonable to expect that this emerging multimodal synergistic therapy guided by CRISPR/Cas9 system will accelerate the development of precise and individualized cancer therapy.