Brain Cancer Treatment with Gene Editing

Abstract

The first method is used gene editing to knock out the PD-L1 receptor located on the T cell surface so that PD-1 on the cancer cell surface cannot combine with the PD-L1, in that case, T cell can identify the abnormal cell and kill it. At the beginning, researchers use protein-guided editing technology, but it is not easy to control and not specific enough, so they choose to use CRISPR-Cas9 to edit the target gene. Comparing with the traditional protein-guided nucleases, CRISPR-Cas9 system is more easy-handle, highly specific, and it is an more efficient tool for engineering eukaryotic genomes; because CRISPR-Cas9 system aims to edit the targeting genes by tiny RNAs guiding the Cas9 nuclease to the target site by base pairing.The second treatment is mainly used “fighting cancer with cancer”.Because living tumor cells have the ability to home and target tumors, thus, if those living tumor cells can be engineered to secrete therapeutic agents, the tumor cells can be effectively cured. Shah’s team picked the agent interferon-β (IFN-β). However, this idea of treatment is limited by the premature cell death due to autocrine toxicity.The researchers solved this problem by first using CRISPR Cas9 to knock out the IFN-β–specific receptor (IFNAR1) in inherently IFN-β–sensitive syngeneic tumor cells, and subsequently engineered them to constitutively produce IFN-β for tumor cell targeting and simultaneous immunomodulation. These therapeutic cells are further designed to coexpress granulocyte-macrophage colony-stimulating factor (GM-CSF) that facilitates the differentiation, proliferation, and recruitment of dendritic cells (DCs). The last approach can stop cancer cell repairing their DNA when it gets damaged.