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CAR-T cell therapy has made great achievements in the past decade, while conventional CAR-T cell therapy also has some obstacles to overcome, such as the CRS and ICANS toxicity, and the expensive and complex manufacturing process. The in-vivo CAR-T cell engineering by nanoparticles carrying CAR genes and gene-editing tools has shown potential breakthroughs in overcoming the above obstacles of traditional CAR-T cell therapies. Therefore, there is more urgent to develop safe and simple in-vivo CAR-T cell engineering solutions.