Part One: Will Phagotherapy Be a New Nemesis for Antibacterial Antibiotics?

Make the Immune Responses of Microorganism Engineered with CRISPR Attack Itself

Genetic modification of virus can lead to bacterial "suicide", which may be the next fight against antibiotic-resistant infections.

According to a report at the 2017 CRISPR Conference held in Montana, USA, several companies have used CRISPR gene editing system to engineer such viruses which were called phages, in order to kill specific types of bacteria. These companies will start clinical trials as early as next year.

Rodolphe Barrangou, chief scientific officer of North Carolina’s Locus Biosciences, said at the conference that preliminary tests showed that these phages rescued the mice that would otherwise had died of antibiotic-resistant infections.

Phages, isolated and purified from nature, have long been used to treat human infections, Eastern Europe in particular. These viruses infect only certain types of bacteria or bacterial strains, and therefore have less impact on the body's natural microbiome than antibiotics. It is generally accepted that they can be used on human beings, and it is totally safe.

However, phagotherapy has been developing slowly. Part of the reason is that these viruses exist naturally and cannot be patented. Bacteria can also rapidly evolve resistance to native phages, which means that researchers must continually isolate new phage that can fight against the same bacterial strain or bacterium. For regulators, it is harder to implement new treatments continuously.

Use CRISPR to Drive Bacterial Death

To avoid these problems, Locus and several other companies are working on phage that will allow the bacterial immune system CRISPR to target itself. Locus's phage targets antibiotic-resistant bacteria whose CRISPR system contains the DNA that can give instructions for a modified guide RNA, which locks on to parts of an antibiotic-resistant gene. Once a phage is infected with a bacterium, the guide RNA "grabs" its resistance gene. This triggers the Cas3 enzyme to destroy the gene sequence, which bacteria normally produce to kill the phage. Eventually, Cas3 destroys all the DNAs and kills the bacteria. "I now find it a bit ironical to use phages to kill bacteria like this," said Barrangou.

Eligo Bioscience, another Paris-based company, also uses a similar approach. It removes all the genetic instructions that allow phage replication and inserts DNA that codes for the guide RNA and the bacterial enzyme Cas9. Cas9 cuts bacterial DNA at the designated site, causing the bacteria to self-destruct. Xavier Duportet, Eligo's chief executive, said that the system's future goal is human intestinal pathogens, but he declined to say exactly what the pathogens are.

About Author

Creative Biolabs is a biotech company located in New York. Since its establishment, Creative Biolabs has been providing custom biotechnology and pharmaceutical services that cover the full scope of biotechnology needs of early drug discovery and development to customers all over the world, such as immunized antibody library phage, scfv phage display library, antibody engineering, etc.

I'm Oliver Ray from LA. I'm interested in writing everything about biotechnology. Hope you enjoy reading my articles.