Recently, the team of Professor Luo Jianhua from the University of Pittsburgh used CRISPR technology to effectively target the fusion of carcinogenic fusion genes, significantly improving the survival rate of invasive liver cancer and prostate cancer mice. This achievement was published in Nature, a subsidiary of Nature Biotechnology.
"This is the first time that gene editing technology has been used to specifically target carcinogenic fusion genes," said Professor Luo Jianhua, author of the article. "This is really exciting because it lays the foundation for a new approach that could become a cure for cancer."
A fusion gene refers to the fact that two originally isolated genes are linked together due to a mutation. Thus, a new gene produced by merging all or part of the original two genes may express a carcinogenic abnormal protein.
â–²How to generate fusion genes (Source: Wikipedia)
Scientists use CRISPR-Cas9 gene editing technology to target unique DNA sequences formed by gene fusion, namely TMEM135–CCDC67 and MAN2A1–FER oncogenic fusion genes. They used an adenoviral vector to deliver the Cas9D10A enzyme and the guide RNA to target the DNA sequence around the fusion point and introduce herpes simplex virus type 1 thymidine kinase (HSV1-tk) with homologous fragments around the breakpoint. The gene is inserted in order to reconnect the two ends of the breakpoint. Thus, only cancer cells carrying the target fusion gene were specifically inserted into the HSV1-tk gene and were observed by the EGFP fluorescent label added to the HSV1-tk gene. When the current drug molecule ganciclovir (ganciclovir) is added, it is phosphorylated by the HSV1-tk enzyme to produce cytotoxic products, which cause apoptosis of cancer cells. It can be seen that if this new treatment idea is successfully applied to the clinic, it will significantly reduce the side effects of cancer therapy.
▲The idea of ​​gene editing carcinogenic fusion gene (Source: "Nature Biotechnology")
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