CRISPR-Cas9 z-bo 2020-09-24 401

　　After scientists established the CRISPR-Cas9 gene editing technology, the technology has been widely used. Some studies have used CRISPR-Cas9 gene editing tools for gene screening, and found some genetic weaknesses in cancer cells that can be used to develop potential treatments.

　　Recently, researchers from the University of Toronto in Canada conducted a genome-wide CRISPR-Cas9 screening in RNF43 mutant pancreatic ductal adenocarcinoma (PDAC) cells and found potential antibody drugs that can be used to treat this type of cancer. This type of PDAC relies on Wnt signaling for proliferation.

　　In this study, the researchers found through screening that a Wnt signaling pathway involving FZD5 is important for the proliferation of PDAC cells carrying RNF mutations. FZD5 is one of the ten Frizzled receptors encoded by the human genome. The research results show that the expression level of the Wnt receptor has background-dependent characteristics. Researchers used a set of recombinant antibodies to detect the expression of FZD protein and confirmed that the functional characteristics of FZD5 cannot be explained by protein expression.

　　In addition, the researchers also found that antibodies that specifically bind to FZD5 and FZD8 can greatly inhibit the growth of RNF43 mutant PDAC cells in vitro, and also have similar effects in tumor xenograft models. This is what they observed during the gene screening process. Functional features provide support. Patient-derived PDAC cell lines carrying RNF43 mutations will also be selectively inhibited by the FZD5 antibody, further indicating that this antibody can be used as a potential targeted therapy for the treatment of PDAC. Researchers also found in tumor organoid culture experiments that colorectal cancer tumors carrying RNF43 mutations are also sensitive to FZD5 antibodies, indicating that the phenomenon discovered based on PDAC has a wider range of potential applications.

　　These results indicate that CRISPR-based gene screening is a powerful tool for discovering genetic weaknesses in cancer cells. It can be used to discover and confirm cell surface targets and develop effective antibody therapeutics.