Scientists use CRISPR technology to eliminate cancerous genes

Scientists use CRISPR technology to eliminate cancerous genes

Release date: 2017-10-09

As a signaling protein in the "downstream region" of intracellular signaling pathways, the KRAS gene acts as a "switch" in the body, and it plays an important regulatory role in the signaling pathways of tumor cell growth and angiogenesis.

For decades, although various treatments targeting KRAS mutant proteins have been tried, no KRAS gene has been targeted. An article published in the September 26 issue of Cancer Research revealed that scientists have made major breakthroughs this time.

Using CRISPR, mutation KRAS tumors are reduced by about 50%

In order to target the KRAS gene, scientists have to "kill" the activity of other genes. In this study, researchers from the University of California, San Diego School of Medicine systematically inactivated all genes in the human colon cancer cell genome using CRISPR-Cas9 gene editing technology.

Subsequently, scientists transplanted human colon cancer cells containing normal KRAS mutant genes and inactivated all genes into mice to test tumor growth. After extensive investigation, it was found to be responsible for the combined efficacy of the NADK and KHK genes encoding metabolic enzymes. When scientists inactivated these two genes, normal KRAS tumors were unaffected, but the growth of mutant KRAS tumors decreased by nearly 50%.

"It is worth noting that we did not see the expected anti-cancer effect in the culture dish. The tumor inhibition effect caused by NADK and KHK gene inactivation only occurred in the mammalian model, which is a very close to the actual tumor survival microenvironment. System." Corresponding author, Professor Tariq Rana of the Moores Cancer Center at the University of California, San Diego Medical School, said.

The effect is consistent with chemotherapy

It is reported that the strategy adopted by Professor Tariq Rana's team is called "synthetic lethality", which aims to only intervene or kill cells carrying mutations.

Previously, the research team used microRNAs libraries to systematically block protein production and look for inhibitors that can synthesize lethal KRAS mutations. They found that the use of CRISPR-Cas9 for a gene-editing method was consistent with the use of commercially available small molecule inhibitors (chemotherapy), resulting in a significant reduction in KRAS mutant tumors in mice.

Unexpected discovery: finding new tumor suppressors

In addition, the Rana team also discovered some new genes: inactivation of them, but can increase KRAS mutant tumor growth, but will not affect the normal tumor of KRAS. These genes are legendary "tumor suppressors" whose presence inhibits cancer cell growth.

One of the newly discovered tumor suppressors was identified as the INO80C coding gene. INO80C is a large multi-subunit protein with a stable genome function.

The Rana team is continuing to explore a large amount of new data they have acquired to understand and decipher the development of KRAS mutant cancer. The ultimate goal is to turn research into effective treatments to prevent tumors. At the same time, he also mentioned the limitations of this study, that is, he suspected that the metabolic dependence of tumor cells growing in the laboratory may be different from the cells growing in the living system.

Source: Bio-Exploration

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