On July 20th, the research team from the University of California, San Diego, and the Massachusetts Institute of Technology published the latest results in the journal Nature, demonstrating their first "gene loop" in bacterial cells and inserting anticancer drug synthesis genes. Make it a "tool" for the synthesis of anticancer drugs.

        The most amazing thing is that these bacteria with special missions can collectively “self-detonate” tumor sites to release anticancer drugs to eliminate cancer cells.

        This bacterium is the result of years of research by the team of bioengineering and biology professor Jeff Hasty. Around this design concept, they have published four related articles in the journal Nature.

        The advantage of this particular bacterium is that it minimizes the damage of the drug to surrounding normal tissues and cells.

Gene loop: limit bacterial growth and achieve collective suicide

       Considering that traditional chemotherapy does not always reach the core of the tumor accurately, but the bacteria can do it, Professor Jeff Hasty of bioengineering and biology began to consider the use of bacteria to achieve drug delivery. But how do you let bacteria control the timing of drug release?

       He led the research team at San Diego to select attenuated Salmonella intestinal subspecies and used synthetic biology to construct a genetic loop in the bacteria. In this genetic loop, bacteria in the tumor microenvironment are able to initiate drug synthesis and lyse at the same time to destroy cancerous cells.

       This magical genetic loop contains a gene encoding the key molecule AHL. The AHL molecule is the master switch that coordinates cellular gene expression. When the concentration of AHL molecules reaches a threshold, the promoter is activated to further activate the expression of downstream genes.

       At the same time, thanks to the small size of the AHL molecule, it can circulate between bacteria, enabling adjacent bacteria to receive the same signal, initiate gene expression, and achieve synchronization. This chain phenomenon is called "quorum sensing."

       Quorum sensing is a way of maintaining "contact" between bacteria. By synthesizing and releasing signal molecules to grasp the number of bacteria, the colony is coordinated at the same "step".

       Scientists are smart, they use this feature to achieve unified management of the bacterial population. More interestingly, they added a suicide gene to the loop, causing the number of bacteria to reach a certain concentration, collectively cracked!

       Of course, a small amount of bacteria will survive and then move on to the next cycle.

Screen the right combination of drugs

       After the problem of simultaneous management of the bacterial population was resolved, the researchers began screening for appropriate anticancer drugs. They selected three medicinal proteins that inhibit tumor growth. It was found that when these three proteins were combined, the drug effect was the best.

       Therefore, they inserted the genes encoding these proteins into the gene loop. The author of the article, Professor Tal Danino, led the team to model cancerous mice and found that this special bacterial group can synthesize enough protein to fight cancerous cells.

       In particular, when this combination of bacterial therapy and chemotherapy, it will show a better therapeutic effect.

     Although this new method has not cured cancer-bearing mice, it can significantly prolong the survival time of diseased mice (about 50%). In the next step, the researchers plan to select the bacteria present in the tumor microenvironment and use synthetic biology to transform and construct a therapeutically useful population.

       At the same time, they will also conduct in-depth research to ensure the stability of the genetic loop within the bacteria and reduce the risk of genetic mutation.

       The realization of this theory is inseparable from "group sensing." Although the current research results are still in animal testing, it is indeed a new and far-sighted approach that provides us with new horizons to fight cancer.

       In summary, this experimental model based on animal models successfully completed the first proof of synthetic biology for the purpose of engineering bacteria and achieving targeted anti-cancer drugs.

Original source: http://cn.chemcd.com/news/30180.html