How GM Viruses Fight Bacteria
CRISPR 2017 Conference
Julia Korowski, XX2 century
In an attempt to cope with the resistance of bacteria to antibiotics, scientists turned to the creation of genetically modified viruses. Last week, the CRISPR Congress 2017 conference was held in the USA – at which specialists of biotech companies presented new developments in the field of bacteriophage treatment. Trials of some drugs will begin next year.
Bacteriophages are viruses that selectively infect and destroy bacterial cells. The idea of using them to fight infections, to put it mildly, is not new – treatment with bacteriophages or "phage therapy" was practiced back in the 20s of the last century, and in Russia has now registered 13 drugs of this kind. Phage therapy is considered safer for the microflora than antibiotics, since viruses kill certain bacterial strains, and not everything that gets in their way. However, in the West, virus treatment was abandoned quite quickly: most of the works were published in Russian or Georgian, the mechanisms of action of viruses were not entirely clear, besides, antibiotics appeared on the market, which are easier to manufacture and store.
But in the XXI century, when the resistance of bacteria to antibiotics became a serious problem, scientists again turned to phage therapy. However, viruses that occur in nature do not satisfy them, because pathogens are able to adapt to them as well. If bacteria developed resistance to a certain type of bacteriophages, doctors would have to look for another species capable of killing the same microbial strain, and the supervisory authority would have to approve new types of treatment over and over again. In addition, natural phages cannot be patented, and this is unprofitable for the pharmaceutical industry.
Biotech companies are developing viruses that tune the CRISPR bacterial system against the bacteria themselves. For example, representatives of the company Locus Biosciences told at the conference that they create phages to fight resistant microorganisms. In their DNA there are sites encoding guide RNAs that disable the gene responsible for resistance. When a virus infects a bacterium, the guide RNA is attached to the resistance gene, and the bacterial enzyme Cas3 – usually the pathogen uses it just to fight viruses – destroys this nucleotide sequence. After a while, Cas3 destroys all the DNA and kills the bacterium.
Specialists of the French company Eligo Bioscience use a similar approach. They cut out all the genes responsible for reproduction from the bacteriophage and embed the DNA that encodes the guide RNAi bacterial enzyme Cas9. Cas9 cuts bacterial DNA at a certain point, and this break triggers the process of self-destruction of microbes. The president of Eligo explained that this virus is designed to fight intestinal pathogens, but did not specify which ones.
Locus and Eligo will begin clinical trials in 18-24 months. At first, they will treat severe infections, but in the future they plan to create phages to "fine–tune" the microflora - theoretically, this will help fight obesity, autism and some types of cancer. At the moment, the links between the microbiota and the listed diseases are poorly understood, but representatives of the companies hope that by the time phage therapy begins to be actively used, this will no longer be a problem. Moreover, they themselves can participate in these studies: if scientists manage to change the microflora of laboratory animals with the help of viruses, it will become clear which strains of microbes affect the development of autism and other abnormalities.
Before treatment with genetically modified viruses enters medical practice, many questions will have to be answered. Most likely, many phages will be needed to treat infections; it is necessary to find out whether they will cause unwanted immune reactions. In addition, it is not known whether the phages themselves can transmit resistance genes to bacteria. We will probably find out the answers soon, because antibiotic resistance forces scientists to look for new options more and more actively.
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23.06.2017