Virus robots are programmed to block human blood vessels and kill cancer.

Blood vessel blockage and tumor tissue necrosis within 72 hours after the injection of the DNA robots into the mouse circulatory system

DNA molecules have proven to be an excellent basis for designing and constructing mechanical molecular devices that can respond to external signals — and perform certain actions depending on them. In recent years, scientists have conducted successful experiments with DNA robots as vehicles and imaging probes. The experiments were carried out in a cultured medium from grown cells, on insects and nematodes Caenorhabditis elegans . But so far, never experiments with targeted drug delivery have not been performed on mammals.

At the same time, from 2003-2005, it is known that a successful strategy for treating cancer is selective blockage of tumor blood vessels in order to deprive it of nutrients and oxygen - and to launch an avalanche of death of tumor cells. DNA robots are perfect for this task. Moreover, this standard strategy works for many types of cancer, since the blood vessels that feed solid cancer tumor cells are essentially the same.

The team of Chinese scientists first conducted such an experiment on mammals (mice). They designed robots using DNA origami and loaded them with thrombin molecules. This is a serine protease, the most important component of the blood coagulation system of humans and animals. Thrombin regulates platelet aggregation by activating platelets and converting circulating fibrinogen to fibrin, which causes a fast blockage of the blood vessel (thrombosis).


Design and description of the nanobot with thrombin. DNA origami reacts to nucleolin and unfolds into a rectangular sheet. It is filled with thrombin molecules, rolled into a tube, and closed in blood vessels in the closed state. Upon arrival at the site of the blockage, the robot reacts to nucleolin, opens up and releases thrombin molecules (bright spots in the photo below taken with a scanning atomic-force microscope, scale mark corresponds to 100 nm)

In order to effectively use this method, it is critical to accurately deliver thrombin to the right place and to block a specific vessel in order to minimize the potential damage to other vessels where no blockage is required. It was not possible to achieve this with traditional methods, so pure thrombin was not used to treat cancer before. Chinese doctors managed to successfully solve the problem with the help of DNA robots. These robots protect thrombin and do not release it until they meet in their path a characteristic marker of a cancerous tumor - nucleolin. When meeting with him, the robots instantly open up and release the “medicine”.

DNA origami method allows you to create a rational design and production of nanostructures of the desired size, shape and functionality. Scientists conducted an experiment on a live mouse with a human breast cancer tumor - and proved the effectiveness of such robots in real use. The robots successfully blocked a specific blood vessel feeding the tumor and did not touch the other vessels.

To prove that robots do not cause harm to larger mammals, additional experiments were conducted on miniature domestic pigs (mini-pigs), which are very similar to humans in anatomy and physiology. The pigs were injected with a standard mouse therapeutic dose of DNA robots (150 units per pig). Since the pigs did not have a tumor, the robots freely circulated in the vessels and did not work. No abnormalities in the circulatory system and blood clotting parameters were observed. Some anomalies were observed when the dose was increased to 350 units, but they turned out to be temporary and thrombosis of vital organs did not occur.


Dwarf domestic pig

As shown in the illustration above, the nanobot is a self-assembled nanotube with several functional elements. It unfolds into a rectangular sheet measuring 90 × 60 × 2 nanometers.

The robot is made of bacterial m13 bacterial genomic DNA. It is a virus that infects Escherichia coli (E. coli). The DNA of this virus is a popular tool for designing various nanostructures. Previously, experiments were conducted with varieties of such robots that are capable of carrying a payload of different proteins. For example, they are used in the process of assembling cobalt oxide nanowires in batteries , as well as for packing carbon nanotubes into dense bundles, which are used in photovoltaics .

Although experiments on humans are still ahead, some experts consider a fundamentally new method of cancer treatment to be a real breakthrough. Selective destruction of cancer tumors looks much more promising than “barbarous” chemotherapy, which destroys all cells in a row. If the drug selectively acts only on tumors and is harmless to a healthy person, then theoretically such a person can take such "injections" with DNA robots as a preventive measure. He has some kind of cancer - the medicine will kill her, if there is no tumor - nothing will happen.

The scientific article was published on January 12, 2018 in the journal Nature Biotechnology (doi: 10.1038 / nbt.4071, pdf ).