Blue and white nano submarines

An Israeli researcher has developed nano-submarines capable of locating individual cells in the body and injecting into them molecules that change the functioning of the cells. The invention may provide treatment for Crohn's disease and other autoimmune diseases, and in the future can be used as a milestone in curing diseases such as AIDS and Huntington's disease.

One of the great dreams of medical science is the development of drugs without side effects. This is no small thing: chemotherapy without side effects, for example, will greatly improve the ability to treat cancer. One way to avoid the side effects of a drug is to transfer the beneficial substances, directly to the cells in our desire to kill or heal. A milestone in the field was recently laid by an Israeli - Dr. Dan Farr and his partners from Harvard Medical School - who managed to develop tiny submarines - a hundred times smaller than human cells - capable of focusing on cells in the body and injecting the drug substances into them.

The invention of Dr. Dan Parr and his partners from the Harvard Medical School, which was published last year in the prestigious journal Science, may be one of the most important steps on the way to a cure without side effects, and even to cure diseases that until now were considered incurable, such as AIDS and Huntington's disease. A few months ago, Dr. Farr opened the nanomedicine laboratory at the Faculty of Life Sciences and the Center for Nanoscience and Technology at Tel Aviv University, where he is working on additional applications for this system in the various fields of cancer and inflammatory diseases and on new systems.

Dr. Parr's invention is based on liposomes - tiny globules composed of fatty acids and coated with molecules that allow them to identify certain cells and penetrate them, or inject the contents of the liposome into them. The liposome can be filled with many different substances, according to the designer's wishes - starting with toxins that can kill the target cell and ending with siRNA, pieces of genetic code that are able to change the functioning of cells in the body.

Although other researchers have previously succeeded in producing targeted liposomes, they could not bypass the body's natural defense system. The immune system immediately senses the small nano-submarines injected into the bloodstream, and acts decisively to eliminate and break them down. Farr's liposomes, on the other hand, are coated with sugars that naturally exist in the body, and are not recognized by the immune system. In addition, the liposomes are coated with proteins capable of binding to the diseased cells, and thus the particles are selectively localized to diseased cells.

If all the innovation was in the invention of stealthy and encapsulated liposomes, we would be sued. But Farr made sure to fill his unique liposomes with molecules that are the future of medicine, according to many good people in the field. The siRNA molecules, whose engineering and correct introduction into the cell can silence existing genes by choice. The siRNA may provide a solution to diseases caused by the action of mutated genes, such as Huntington's disease and cancer, and is even able (as a 2008 study showed) to stop viral diseases, such as HIV, by stopping the replication mechanisms of the virus inside the cells. The only problem is that the siRNA molecule breaks down easily in the bloodstream, so it needs a carrier to bring it to the right cells, and these are Parr's nanosubmarines.

"We have developed particles that are made of completely biodegradable material, which the body does not recognize and is unable to develop an immune response against. The particles are like submarines - a kind of transport system - that sail, homing very quickly on their target - an integrin that is only found on the cells of the immune system and especially the T cells of the intestine." Parr explains. "We showed that as soon as they stick to the target, they enter it and release the siRNA into the cell. We showed this by using an intravenous injection, and we were the first to show that it is possible to selectively manipulate the cells of the immune system and that the nanoparticles know how to home in only to these cells and not to other cells."

Parr and his research partners injected laboratory mice with the nanosubmarines, which were 'programmed' to stick to cells in the intestinal immune system and inject the siRNA into them. Within the cells of the immune system, the small molecule caused the cells to stop dividing, and did not allow them to produce an inflammatory reaction in the intestinal area. Such treatment may be particularly effective against Crohn's disease, which is caused by overactivity of the immune system cells in the intestine. In addition, the siRNA can be designed so that it does not affect other cells, even if it accidentally reaches them. It is, in fact, a medicine without side effects.

What is the future of the method? Parr is cautious, but optimistic. "It's hard to know what will happen, because there is no product on the market yet. But the whole discovery of the siRNA was in 1998, just over ten years ago. This is a very, very young science... I hope, like all others, that it will lead to the development of new drugs. There is enormous promise for this field. At the moment, major companies in the world are working in this field on cancer, autoimmune diseases, neurodegenerative diseases and diseases caused by viral infection such as HIV, Sars, Nile fever, etc."

According to Parr, the new science of nano-submarines is gaining momentum all over the world, and especially in Israel. "In nanomedicine, I think Israel is a powerhouse, especially in the medical direction. There is a very large activity in Israel. One of the first medical nano-carriers in the field of chemotherapy - Doxil - was invented in Israel by Prof. Yehezkel Bernholtz and Prof. Alberto Gavizon from the Hebrew University. There are many other researchers - also at the Hebrew University, also in Tel Aviv, also at the Technion and Ben-Gurion. Overall, we are considered a power because a lot of this push comes from Israel."

Even when the first drugs based on siRNA hit the market, it is likely that their price will skyrocket, because the production cost of siRNA is relatively high compared to conventional drugs. But as is the way of new technologies, there is reason to believe that with the development of new work methods, creative solutions will also be found to the cost problem. Does the future hold cures for AIDS, cancer and genetic diseases? for siRNA solutions.

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