In a huge scientific milestone, scientists at the Innovative Genomics Institute, or IGI, harnessed a new CRISPR technology that can be used to engineer bacteriophages, which has been a long-time challenge for scientists due to the diverse defense systems that protect their genomes.
The study was published Oct. 31 in Nature Microbiology and was authored by scientists at IGI. Lead author and campus postdoctoral researcher Benjamin Adler stated that the research team resourced a CRISPR system called Cas13, an RNA-guided RNA targeting Cas protein. The new technology could help address urgent challenges in human health, bioenergy and agriculture.
“Cas13 is a single protein that is reliably able to edit some of the most abundant organisms on earth,” Adler said. “Because these viruses are natural predators of bacteria, this opens avenues to develop novel medical and eliminate agricultural therapeutics.”
Bacteriophages are viruses that infect bacteria, and bacteria have developed ways to resist infection, according to Vivek Mutalik, a scientist at Lawrence Berkeley National Lab and a co-author of the study. CRISPR is one such defense system that bacteria use to deactivate infections. In response, bacteriophages have evolved and developed ways to overcome these defenses over millions of years.
Due to the diverse modes of defense used by bacteriophages to protect their DNA, Mutalik noted that it has been a challenge for scientists to engineer them.
He stated that the study shows how researchers can design a specific stretch of RNA molecules that can bind to a particular region on the phage RNA, which Adler noted was a surprisingly exposed molecule during infection. After binding, the Cas13 protein causes target RNA degradation and stops the growth of the infected bacteriophage.
The authors of the study demonstrated how to use this tool for engineering bacteriophages “at a scale that has not been done before,” according to Mutalik.
He added that scientists hope to engineer bacteriophages in order to address human infectious diseases that are resistant to antibiotics and to protect crops from infectious agents, among other potential uses.
“It’s a huge milestone in phage biology and phage engineering field,” Mutalik said in an email.
Mutalik noted that this is an exciting time for students to understand the technology and its implications on the future of biotechnology, adding that phage research and microbial biotechnology give students simple ways to learn about bacteria and viruses, their role in our everyday life, the complexity of microbiomes and their role in the world around us.
The next challenge is to demonstrate that it works across a greater diversity of bacteriophages that infect other bacteria, rather than just the lab bacterial strain used in this study, Mutalik said.
“We would like to be able to extend this technology to additional bacteria, say, for instance, medically relevant pathogens, and to be able to edit those bacteriophages,” Adler said.