Potential gene editing tools found in thousands of viruses

A major study led by Professor Jennifer Doudna, a pioneer in the field of gene editing, has recently been published online in the leading academic journal Cell, and has attracted the attention of many journals, including Nature and Science.

The new research uncovers a plethora of potential CRISPR-based gene editing tools in thousands of viruses. Several experts noted in a review article that the new study is "an important step in the discovery of the enormous diversity of the CRISPR-Cas system" and "opens the door to possible new CRISPR system applications."

Professor Jennifer Doudna of the University of California, Berkeley, won the Nobel Prize in Chemistry in 2020 for her discovery of the CRISPR gene editing system. She and her collaborators discovered in 2012 that CRISPR found in bacteria and archaea can be used for genome editing.

This system is commonly used in bacteria and archaea to defend against viral infections. It is made up of special CRISPR sequences, CRISPR-associated proteins, and RNA that can capture invading viruses' genomic fragments and store the sequences in their own genome so that when they encounter the same virus again, they can recognize and cut the corresponding DNA.

With the scientists' modifications, the bacteria's immune system can be used to precisely target specific DNA sequences and then targeted to cut away, allowing for efficient genome editing.

Professor Doudna and colleagues Professor Jillian Banfield and others discovered in the new study that some viruses in nature have "stolen" this gene shearing system from the bacteria they infect. The team discovered over 6,000 viruses with the CRISPR system after conducting a thorough search of the viral genome.

All six known CRISPR-Cas types are covered by these newly discovered CRISPR systems. These CRISPR systems in viruses exhibit a wide range of variations when compared to the general CRISPR-Cas structure. Some are missing key components, whereas others are more compact.

Among the various types of viruses, those that use bacteria as hosts are referred to as phages. Bacteria's antiviral system is the CRISPR system. What is the purpose of the CRISPR system that phages acquire from bacteria in order to use against themselves?

The most likely reason, according to Prof. Doudna's analysis, is to outperform the competition. This is due to the fact that multiple viruses may attack the same bacteria at the same time, resulting in "phage wars" within infected cells. Bacteria are also susceptible to plasmids, which force them to replicate the plasmid's DNA strands. Phages that "steal" the CRISPR system from their bacterial hosts can destroy their competitors, leaving the bacteria to provide only their own services.

What's most intriguing about this discovery is that the CRISPR system in phages has a unique advantage when it comes to genome editing—the Cas enzyme used by the virus to cut DNA is very small, and the smaller enzyme can be delivered to the cell more easily.

Some of the new CRISPR-Cas enzyme sources identified in this study have also shown genome editing potential in a variety of cell types, including human and plant cells (such as Arabidopsis and hexaploid wheat).

Professor Doudna stated that while some smaller Cas enzymes have been discovered in nature, they have so far been inefficient for genome editing applications. Some viral Cas enzymes, on the other hand, combine the advantages of being small and efficient.