A study published in 2023 in “Science” developed CRISPR-Cas9-engineered EcN that specifically recognizes low-oxygen signals in the TME and secretes anti-tumor cytokines (such as TNF-α and IL-12) in situ, significantly inhibiting tumor growth in a mouse colorectal cancer model (with a tumor inhibition rate of 78%) while reducing toxicity to normal tissues (86). Here, TNF is linked to colorectal cancer.