CD19 and leukemia: To illustrate, plasmid DNA that encodes both interleukin 6 short hairpin RNA (IL-6 shRNA) and CD19-CAR was loaded into anti-CD3-LNPs, and the LNPs enabled the generation of CAR T cells with IL-6 gene knockdown in vivo, which not only killed the CD19-highly expressed leukemia tumor cells but also alleviated cytokine release syndrome (CRS) caused by IL-6.