Release date: 2016-07-27
This research is really cool!
Indeed, I have not seen such a clever design for a long time.
Recently, the official website of the University of California, San Diego (UCSD) and the Massachusetts Institute of Technology (MIT) also released an important news. The research team led by UCSD's Jeff Hasty and MIT's Sangeeta Bhatia have been excited in the field of cancer treatment. The progress of the human heart.
Jeff Hasty of Jeff HastyUCSD of UCSD
The engineered Salmonella developed by them can be directed to release tumors from tumor tissue. They applied this engineered bacteria and traditional anticancer drugs to mice with advanced liver cancer. They were surprised to find that the tumors were shrinking and the survival time of the mice was significantly prolonged. This effect was used alone than any drug. Must be effective.
Sangeeta Bhatia of Sangeeta BhatiaMIT at MIT
For their research results, the industry has used these words to express their feelings. It is an unconventional, very promising, fascinating and refreshingly beautiful concept.
In fact, the research led by Hasty and Bhatia has opened up a promising research direction for refractory cancer.
In recent years, although various immunotherapy for cancer have emerged in an endless stream, for many malignant solid tumors, researchers are still at a loss. First, because there are no blood vessels in the depths of solid tumors, general drugs are difficult to reach; second, solid tumors will continue to evolve and have the ability to dispel the body's immune system, and immunotherapy will take it. How to break into the interior of a solid tumor becomes a problem that plagues researchers.
In fact, researchers have long noticed that because solid tumors have the ability to dispel the body's immune system, there are always a handful of bacteria (such as Salmonella) running to "trust" solid tumors in order to avoid the killing of human immune cells.
Bhatia believes that tumors provide a friendly living environment for certain bacteria, and we are taking advantage of bacteria. Hasty also said that some bacteria have evolved the ability to survive in tumors.
Since 1890, researchers have been trying to use specific bacteria to break into the interior of the tumor, or to directly attack bacteria inside the tumor. However, those attempts either have no effect, or the bacteria destroy the tumor too fast and the body is unbearable.
Hasty and Bhatia also use Salmonella, which lives in tumors, to bring anticancer drugs into the tumor.
Hasty and Bhatia have created three engineering Salmonella with special skills that produce three anticancer drugs. A molecule that produces hemolysin, the molecule's skill is to destroy tumor cells by destroying the cell membrane of the tumor. The second produces a protein that starts inside the cancer cell and induces cancer cells to commit suicide. The third type produces another protein that activates the body's immune system and mobilizes human T cells and DC cells to surround the tumor. Each type of Salmonella can be used in a single operation or in a joint operation to achieve a sea, land and air-type three-dimensional strike inside and outside.
How can such a violent hunting operation developed by Hasty and Bhatia not repeat the mistakes of the predecessors? The innovations of Hasty and Bhatia research are here. They cleverly added a genetic loop in Salmonella, and the design of this genetic loop is simply a slap in the face.
As early as the 1960s and 1970s, scientists discovered the language of communication between bacteria. The researchers found that bacteria can release signaling molecules (AHL, etc.) into the environment. They can understand the changes in the number of external microorganisms by sensing the concentration of signal molecules in the environment. When the concentration of signal molecules reaches a certain threshold, the growth and behavior of all bacteria It will tend to be consistent. For example, collective release of toxins (to resist foreign enemies), "sleeping" (to resist harsh environments), or suicide (controlled by Hasty and Bhatia!). Scientists gave this phenomenon a name called group effect.
Comic
In fact, this phenomenon can be used as an analogy with human behavior. When humans feel that population growth is too fast, the relevant departments will issue a "family planning" policy to allow everyone to control birth at the same time.
This genetic loop designed by Hasty and Bhatia is a clever use of this group effect mechanism. They first installed an expression system that produces signaling molecules for Salmonella, allowing it to continuously generate the signal molecule AHL. Then, a suicide system controlled by AHL concentration is installed on Salmonella. When the system senses that the external AHL concentration reaches the threshold, the suicide system is activated. As a result, a system to control the number of Salmonella populations in the project was created.
Once the engineered Salmonella perceives that their total number reaches a critical value, these engineered bacteria initiate synthetic anticancer drugs and self-destructive patterns, collectively lyse, and all of their killers are made at once. Every time you commit a collective suicide, about 10% of the engineering bacteria will survive. They are the kind of fire that will launch the next round of offense. Under normal circumstances, after 18 hours, they will breed enough and immediately start a new round of offensive.
Under the microscope, the suicide scene of the engineered bacteria caused by quorum sensing was observed. In order to facilitate the observation, Hasty and Bhatia added the green fluorescent protein gene to the engineered bacteria. When the engineered bacteria grows to a certain amount, the AHL concentration in the environment reaches a threshold, and green fluorescent protein synthesis and bacterial lytic protein synthesis are initiated. Under the fast lens, every time the green light flashes, it is like the fire of the original, 90% of the bacteria disappear instantly. The remaining 10% began to multiply again, and it was a flash of green light. So cycle back and forth.
However, from their research, this treatment is currently only available for liver cancer. Because the liver has a filtering effect on bacteria in the blood, and Salmonella is an anaerobic bacterium, it also actively chooses the internal survival of hypoxic tumors.
The researchers also found that engineered bacteria that escaped from liver tumor tissue were quickly cleared by the body's immune system, so essentially all of the engineered bacteria were concentrated in the tumor. This will greatly reduce the side effects of the therapy.
In the mouse experiment, Hasty and Bhatia found that after feeding the mice with a mixture of three engineering bacteria, the bacteria quickly reached the liver tumor tissue of the mice, forming an internal and external pinching action on the tumor, prompting the tumor. Stop growing. If chemical drugs are applied at this time, the tumor tissue will be significantly reduced, and the lifespan of mice will be extended by more than 50%.
Although Hasty and Bhatia are designed to be ingenious, they have no good solution for other tumors. But they also try to develop treatments for other tumors by increasing the dose of bacteria or injections, directly into tumor tissue, and looking for tumor-specific bacteria.
Hasty said that before using this method in the human body, they still have a lot of questions to think about. They also know that the success of mice does not mean that the same results can be achieved in humans. For the current research results, he and his team are very restrained. There is also no signal to release clinical studies.
Source: Singularity Network
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