CRISPR Tools in Viruses Could Accelerate Gene Editing

CRISPR Tools in Viruses Can Accelerate Gene Editing
CRISPR Tools in Viruses Can Accelerate Gene Editing - Phages (seen here attacking a bacterial cell) can use CRISPR-Cas systems to compete with each other or manipulate gene activity in their hosts.Credit: Biophoto Associates/SPL

Viral genomes have been extensively studied, revealing a wealth of CRISPR-based genome editing tools.

WHAT IS CRISPR-CAS9?

“Technology That Can Operate on DNA” CRISPR-Cas9, also known as the 2020 Nobel Prize in Chemistry, is an application that creates excitement in the scientific world. In its shortest and most accurate form, CRISPR-Cas9 is a genome editing tool. In other words, it is a unique technology that allows geneticists and medical researchers to add, remove or alter the DNA sequence. CRISPR-Cas9, which is faster, cheaper and more accurate than any of the techniques used to date, also has a wide range of applications.

It is possible to examine the elements that make up CRISPR-Cas9, which is the simplest, most versatile and sensitive technique currently available among genetic manipulation methods, as follows:

CRISPR stands for “Clustered Regularly Interspaced Palindromic Repeats”. Although there is no clear translation of the definition in Turkish yet "Regularly Spaced Palindromic Repetition Sets" possible to convert.

If we go back to our article;

CRISPR-Cas systems are common in the microbiological world of bacteria and archaea and often help cells fight viruses. However, 23% of the publicly available genome sequences of viruses that can infect these microbes contain CRISPR-Cas systems, according to a study published November 0,4 in Cell. Researchers believe viruses use CRISPR-Cas to compete with each other and perhaps manipulate the host's gene activity to their advantage.

Some of these viral systems have the ability to alter the genomes of plants and mammals, and have qualities such as compact structure and efficient organization that can be useful in the laboratory.

According to computational biologist Kira Makarova of the US National Center for Biotechnology Information in Bethesda, Maryland, "this is a huge step forward in the identification of the enormous diversity of CRISPR-Cas systems." “A lot of innovations were found here,”

CRISPR-Cas is most commonly used in the lab to modify genomes, but it can also act as an essential immune system in the natural world. CRISPR-Cas systems are present in 85% of the sampled archaea and approximately 40% of the bacteria sampled.

These microorganisms often have the ability to take over parts of a virus's genome and store the sequences in a portion of their genome known as the CRISPR sequence. Then, using the CRISPR sequences as templates, RNAs are made that instruct CRISPR-associated (Cas) enzymes to cut the appropriate DNA.

By slicing viral DNA in this way, sequence-carrying microorganisms can prevent viral infections.

Researchers had previously discovered isolated instances of CRISPR-Cas in viral genomes. Viruses occasionally ingest small pieces of their host's genome. If the stolen DNA fragments give the virus a competitive advantage, it can be stored and subtly modified over time to better suit the viral lifestyle.

For example, the DNA encoding the antiviral defense of the bacterium Vibrio cholera has been cut and rendered inoperable by a virus using CRISPR-Cas.

Jennifer Doudna and Jillian Banfield of the University of California, Berkeley, both molecular biologists, decided to further investigate the CRISPR-Cas systems in phages, which are viruses that infect bacteria and archaea. They were shocked to discover that there are about 6.000 of them, including examples of all known CRISPR-Cas systems. According to Doudna, “Evidence suggests these are useful mechanisms for phages.”

The researchers discovered a wide variety of variations in the typical CRISPR-Cas structure, some lacking essential components and others remarkably compact. According to Anne Chevallereau, a researcher focusing on phage ecology and evolution at the French National Scientific Research Center in Paris, “phage-encoded CRISPR-Cas systems, while rare, are extraordinarily diverse and widely spread.”

Because viral genomes are usually small, some viral Cas enzymes are quite small. This can be particularly advantageous for genome editing applications, as smaller enzymes are easy to transport into cells. According to Doudna and colleagues' research, the genomes of cells grown in the laboratory from cress (Arabidopsis thaliana), wheat, and human kidney cells can all be edited using some small Cas enzymes discovered in a group known as Cas.

The findings mean that viral Cas enzymes could join the expanding suite of gene editing tools found in bacteria. Doudna claims that while more small Cas enzymes are found in nature, most of them have so far shown to be rather ineffective for genome editing applications.

In contrast, several viral Cas enzymes are both compact and highly efficient.

In the meantime, the researchers will continue to look for potential improvements to existing CRISPR-Cas systems in microorganisms. Makarova anticipates that the researchers will also look for CRISPR-Cas systems incorporated into plasmids, that is, strands of DNA that can pass from one microbe to another.

Source: nature.com/articles/d41586-022-03837-8

Günceleme: 25/11/2022 13:25

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