A few years ago, the advent of CRISPR technology marked a major breakthrough in science. Derived from a component of the bacterial immune system, CRISPR is able to precisely cut double-stranded DNA, allowing scientists to modify specific genes in plants, animals and humans. This precision makes CRISPR a leading tool for developing treatments for genetic and acquired diseases.
The work depicts the cleavage process of different single-stranded DNA sequences by different bacterial homologues in the novel Ssn enzyme family. Photo credit: Ella Maru Studio
Recently, Professor Frédéric Veyrier and his team at the French National Institute of Scientific Research (INRS) developed a new genetic tool based on the Ssn enzyme family. Unlike CRISPR, this tool targets and cuts only single strands of DNA, taking gene editing to a new level of specificity. Their findings were recently published in the journal Nature Communications. This major breakthrough reveals a key genetic mechanism that could revolutionize numerous biotechnological applications.
Single-stranded DNA is less common than double-stranded DNA. It is commonly found in certain viruses and plays a key role in certain biological processes, such as cell replication or repair. Single-stranded DNA is also used in many technologies (sequencing, gene editing, molecular diagnostics, nanotechnology).
To date, no endonucleases (enzymes that cut DNA) have been described that specifically target single-stranded DNA sequences, which poses an obstacle to the development of technologies based on such DNA.
Now, Professor Veyrier's team has discovered for the first time in the laboratory a family of enzymes capable of cutting specific sequences in single-stranded DNA: the Ssn endonuclease family.
To achieve this goal, the research team at the INRS Armand-Frappilsant Biotechnology Research Center first identified a new family of endonucleases called Ssn in the GIY-YIG superfamily. More specifically, the researchers focused on an enzyme in the bacterium Neisseria meningitidis, also known as meningococci. The enzyme targeted by this study is critical for the exchange and change of genetic material that affects the evolution of organisms.
"During the course of our research, we discovered that it recognizes a specific sequence that appears multiple times in bacterial genomes and plays a key role in the natural transformation of bacteria. This interaction directly affects the dynamics of bacterial genomes," explains Professor Veyrier, an expert in genomic bacteriology and evolution.
In addition to this fundamental discovery, INRS research scientists have discovered thousands of other similar enzymes. "We showed that they are able to recognize and specifically cleave their own single-stranded DNA sequence. So, thousands of enzymes have this property, and each has its own specificity," added Alex Rivera-Millot, a postdoctoral researcher in Professor Veyrier's group and co-first author of the study.
These results represent a new tool for DNA recognition and exchange and are of great significance. They pave the way for many new applications in biology and medicine. On the one hand, understanding this mechanism could lead to better control of relevant bacteria and their associated infections.
On the other hand, the discovery of single-stranded DNA-specific enzymes has made it possible to develop more precise and efficient genetic manipulation tools. This could improve methods of gene editing, DNA testing and molecular diagnostics. These enzymes can also be used for DNA detection and manipulation in a variety of medical and industrial applications, such as pathogen detection or genetic manipulation for medical and therapeutic purposes.
All of these avenues hold great promise for solving many health problems. Currently, the results of this research are pending for a patent.
Compiled from /scitechdaily.com