16 January 2013

Aptamers protect oncolytic viruses from the immune system

Scientists have found a "weapon" that helps viruses in the fight against cancer

Natalia Reznik, InformnaukaThe cell has a deadly enemy – a virus.

In many laboratories around the world for decades, scientists have been trying to adapt strains of different viruses for the selective destruction of cancer cells and even achieve local success in this field, but it is too early to talk about the high efficiency of the method. One of the main obstacles in the development of such anti–cancer viral therapy is the patient's immune system. It does not react to "own" cancer cells, but destroys life-saving, but alien viruses.

The original solution to this problem was proposed by researchers from the University of Ottawa, Krasnoyarsk State Medical University and the American biotherapeutic company Jennerex Biotherapeutics. Its essence is in the synthesis of short sequences of DNA aptamers that selectively bind to antibodies to viruses and "turn them off", so that viruses safely reach the tumor. The patient's immune system does not suffer at the same time.

Aptamers bind antibodies, allowing the vesicular stomatitis virus to infect the cancer cell

As the object of the study, the scientists chose the vesicular stomatitis virus. This is one of the oncolytic viruses (i.e., a virus that selectively penetrates into tumor cells, multiplies in them and comes out, and the cells left by it die), affecting mainly rodents, cattle, pigs and horses, but people can also get infected with it. Specialists have selected aptamers that bind to antibodies to the vesicular stomatitis virus. The project was led by Maxim Berezovsky, a graduate of Novosibirsk State University, now working in Canada.

"Antibodies turned out to be a very "capricious" object, and in order to achieve positive results, non–standard approaches were needed," she noted in an interview STRF.ru Anna Zamai, Candidate of Biological Sciences, is a participant of the project from the Russian side.

However, scientists have managed to synthesize aptamers that selectively bind to antibodies to the vesicular stomatitis virus. Antibodies to the virus are synthesized by B cells of the immune system. Some of the antibodies are dissolved in plasma and interact directly with the virus. The other part attaches to the surface of B-lymphocytes and performs the functions of a receptor. When the receptors "notice" the virus, the cells multiply and intensively synthesize antiviral antibodies. Aptamers synthesized by Canadian and Russian researchers bind to both free antibodies and cell membrane receptors, creating a "breathing" shell around them that interferes with virus recognition. So aptamers prevent both the mass synthesis of the corresponding antibodies, and, as studies performed on cell cultures have shown, their binding to the virus. Scientists hope that aptamers injected in the required amount into the patient's body will be able to neutralize antibodies and increase the circulation time of oncolytic viruses in the blood.

In addition, the researchers have developed electrochemical sensors based on aptamers, which will determine the number of live viruses in the blood, as well as a simple system for cleaning oncolytic viruses from various impurities, again based on aptamers.

"Work with oncolytic viruses continues," says Anna Zamai, "because there are real people, cancer patients, who really need our results. Now we are modifying aptamers to make them more stable in blood plasma. We also started experiments on animals, their first results showed that aptamers are not toxic and not immunogenic for mice. It is hoped that the use of aptamers in antitumor therapy will be safe enough."

Source of information: Darija Muharemagic et al., Anti-Fab Aptamers for Shielding Virus from Neutralizing Antibodies.
Journal of the American Chemical Society, 2012, 134, 17168-17177.

Portal "Eternal youth" http://vechnayamolodost.ru16.01.2013

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