Core Viewpoint - The article discusses a novel approach to overcoming tumor resistance to traditional therapies through a CRISPR-based nano-vaccine (AVAX) that targets the HO-1 gene, enhancing the efficacy of photodynamic therapy and activating anti-tumor immunity [3][4]. Group 1: Research Findings - The study published in Nature Biomedical Engineering presents a CRISPR-Cas9 based nano-vaccine (AVAX) that effectively knocks out the HO-1 gene, reversing tumor cell resistance to reactive oxygen species (ROS) and significantly improving photodynamic therapy outcomes [3][4]. - AVAX demonstrated a 20.15% gene editing efficiency for HO-1 in B16F10 melanoma and LL/2 lung cancer models, leading to enhanced photodynamic therapy efficacy and the induction of an autologous vaccine effect [6][8]. - The combination of AVAX and photodynamic therapy achieved a tumor suppression rate of 93%, with edited ROS-sensitive phenotypes being heritable in progeny tumor cells [8]. Group 2: Mechanism and Efficacy - The AVAX platform utilizes a core-shell self-assembly structure for efficient delivery of the CRISPR-Cas9 system, targeting the ROS resistance gene HO-1 [6]. - When combined with PD-L1 antibodies, 50% of tumor-bearing mice exhibited complete tumor regression, with survival extending beyond 50 days [8]. - The treatment led to a significant increase in CD8 T and CD4 T cell infiltration in tumors, while reducing immunosuppressive myeloid cells [9]. Group 3: Safety and Implications - Safety assessments indicated that the nano-vaccine did not exhibit significant toxicity to major organs, and no off-target editing was detected in immune cells [9]. - This research integrates gene editing with immune activation, achieving a strategy of "enhanced sensitivity and reversal of resistance" in tumor treatment [9].