Bacteriophages have opened many possibilities in the fields of microbiology and biotechnology; both natural and modified phages alike. Natural phages are still being studied by some, whilst others are focusing on finding ways to utilize the unique biology of bacteriophages to create new therapies, some of which go beyond fighting bacteria.
The field of genetics has been developing immensely and has opened many possibilities in phage therapeutics. The modification of phage genetic material has become of interest for many reasons. Some of the most common are;
- bacteriophages can be aimed towards very precise genetic material
- bacteriophages can focus on a combination of genetic materials
- genetically modified phages can be patented
There are currently many companies and researchers working on projects that are looking into many different methods of using modified bacteriophages in therapy. The two most common research projects are those trying to address the growing problem of superbugs and the use of modified phages to target cancer cells.
Modified bacteriophages against superbugs
Although not highly spoken of, ESKAPE has been a problem that has not gone away. In fact, every day it only becomes a strong issue of tomorrow. ESKAPE, an acronym for the 6 bacterial pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) which are highly resistant to antibiotic treatment, and which represent the commonly used term superbugs.
Phage therapy is commonly used against antibiotic-resistant bacteria, even in combination with antibiotic treatment. Research in modified phages has also shown great promise in adjusting the ‘recipe’ or genetic material that a phage would naturally target. Making changes to that material, to be more specific towards which type of genetic material to target can result in genetically modified phage therapy to be even more precise.
Such adjustments to what genetic material a bacteriophage shall target also allows the phage to target more than one type of bacterial genetic material. This would be especially useful for patients who may suffer from the presence of multiple strains or types of highly resistant bacterial pathogens.
Modified bacteriophages against cancer
Modified bacteriophages in cancer treatment seems to be an area of great interest. There are a number of approaches, one of which involves phages to be genetically modified to target specific proteins that are only found in cancer cells, ignoring other healthy cells entirely. Once such a protein is detected, the bacteriophage would continue its natural cycle, in which it would destroy the cell from within.
Another popular research approach is that of identification. Once the immune system comes in contact with the modified bacteriophage, it is able to identify cancer cells that contain the recognizable phage, therefore allowing the immune system to recognize and destroy. This approach is one in which the bacteriophage would act as a signal for the immune system to detect cancer cells which would otherwise escape detection.
Modified bacteriophages as a drug delivery system
Another research towards modified bacteriophages is one where phages are genetically modified to target specific cells and deliver drugs to them. Such a therapeutic approach can certainly change the nature of treatments in the long run. Not only would this provide a perfect mechanism to deliver specific drugs, in specific dosages to the exact location, rather than flushing the entire system with drugs. It can also help to build individualized treatments, as opposed to a ‘one drug fits all’ approach, as has been in the past.
Modified bacteriophages as a vaccine
With the race to find a vaccine against COVID-19, some researchers are also expanding their search by looking into phages as the foundation for such a vaccine. Such a vaccine can act on multiple levels including the adjustments to viral mutations and the bacteriophage’s unique biology to activating and boosting immune response. Phage-based vaccines also provide versatile paths for administration; including injections as well as oral and nasal sprays.
There are many other studies in this field, including the use of modified phages in a more traditional approach, to help spark an immune response. With such a diversity of research, one thing is for certain, the discovery and nature of bacteriophages have opened many possibilities in a number of fields.
Companies focusing on modified phages
- TechnoPhage – Portugal
- PhagoMed – Austria
- Eligo Bioscience – France
- Pherecydes Pharma – France
- BiomX – Israel
- LyseNTech – Korea
- Locus Biosciences – USA
- Adaptive Phage Therapeutics – USA
- Sensei Biotherapeutics – USA
- Intralytix – USA
- Armata Pharmaceuticals – USA
It has been noticed that in the past year many of these projects have been given the green light towards taking their research onto the next phase, as well as the growth of new companies investing their resources into this field. It is unclear whether we have finally come to the next stage of changing our approach to therapeutics, or whether antibiotic resistance may be a much bigger threat than we thought. However, regardless of the reasoning, phage therapy, be it with the use of natural bacteriophages or genetically modified phages, will certainly change medicine and the way we approach treatment.