Release date: 2017-08-16 With the continuous maturity of CRISPR gene editing technology, more and more scientists who are struggling at the forefront are beginning to explore its unlimited application potential. Last week, we reported two related news: a study assisted by Professor Zhang Feng used CRISPR technology to find a gene related to cancer immunotherapy; Dr. Yang Wei’s team used this technology to make endogenous sources in pigs. The inactivation of the viral sequence solves a major problem in xenotransplantation. Professor Sidi Chen, one of the leaders of this study (Source: Yale University) Today, a team of professors from the Institute of Systems Biology at Yale University collaborated with Professor Randall Platt of Switzerland to find key mutations in glioblastoma using CRISPR technology. The study was published in the journal Nature Neuroscience. Glioblastoma is a malignant brain tumor that is extremely difficult to treat. It is estimated that after diagnosis, about half of the patients can only live for 1-1.5 years. Unfortunately, we have no good way to treat this disease, and even the reasons behind it are not clear. Currently, biologists know that more than 223 genes are involved in the disease. But we don't know which genes, or which combinations of genes, cause these cancers. This is also the research focus of Professor Chen's team. At Yale University, Professor Chen's research focuses on developing new tools and applying them to the next generation of cancer genetics, genomics, and systems biology. These tools can help solve a range of problems such as cancer, progression, and metastasis, and provide insight into potential treatment options. Screening method for this study (Source: "Nature Neuroscience") In order to find genetic mutations that lead to glioblastoma, Professor Chen developed a new screening tool using CRISPR gene editing technology. First, they found genetic mutations common in human brain cancer in the database and constructed a set of sgRNA libraries for CRISPR editing. Subsequently, they used adeno-associated virus (AAV) technology to introduce these systems that mutate specific genes into the mouse brain. Later, they observed whether these mice developed symptoms of glioblastoma. From these morbid mice, researchers can reverse which gene mutations will induce this fatal brain tumor. As they expected, many mice developed glioblastoma. For subsequent sequencing analysis of these brain tissues, the researchers found that some genetic mutations are particularly common. Pten, Nf1, B2m, Trp53 and other genes involved in cell cycle, immune regulation, and DNA repair and replication, the frequency of mutations is more than 70%. These results suggest that these genes may play a key role in the pathogenesis of glioblastoma. Some genetic mutations are common in tissue samples (Source: Nature Neuroscience) Because of the efficiency and precision of CRISPR technology, researchers can mutate multiple genes at once. This also allowed them to analyze the effects of different combinations of genetic mutations in glioblastoma. In the analysis, the researchers evaluated a total of more than 1500 mutation combinations. Among them, the combination of B2m–Nf1, Mll3–Nf1, and Zc3h13–Rb1 is considered to be the main common driving factor for brain tumor induction. In addition to identifying potential carcinogenic factors, the study also provided insights into treatment. Researchers want to know if these genetic mutations will affect the treatment of brain tumors. Therefore, they underwent temozolomide chemotherapy for different mutant mice to observe the therapeutic effects of these mice. It was found that mice with Zc3h13 or Pten mutations responded poorly to chemotherapy. This may provide a new idea for the treatment of glioblastoma - if the patient has these mutations, the doctor should consider treatment options outside of chemotherapy. Glioblastoma, a chronic disease, is expected to usher in an individualized treatment plan (Source: Wikipedia) "We have sequenced the human cancer genome, and thousands of new gene mutations have been linked to cancer. But it has been difficult to prove which genes, or which combinations of genes actually cause cancer," Professor Chen said. "Now, We can use this information to determine which drugs are most likely to have a good effect on individual patients. This is a step closer to individualized cancer treatment." We congratulate Professor Chen on the successful publication of the results of the research team, and I wish their tools can help find more new targets for cancer treatment and bring better treatment options for patients. Reference material [1] AAV-mediated direct in vivo CRISPR screen identification functional suppressors in glioblastoma [2] From thousands of suspects, Yale researchers ferret out cancer-causing genes Source: Academic Jingwei Polarizing Microscope ,Polarized Light Microscopy,Polarized Optical Microscopy,Polarised Light Microscopy Ningbo ProWay Optics & Electronics Co., Ltd. , https://www.proway-microtech.com