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Understanding CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)
For many bacteria, one line of defense against viral infection is the RNA guided “immune system” known as CRISPR-Cas. This particular complex is unique because of its ability to recognize viral DNA and trigger its destruction. Scientists have used CRISPR to degrade sections of viral RNA and use the CRISPR systems to remove unwanted genes from an organism. CRISPR proteins have also been studied with the hope of eliminating serious disease and illnesses. However, this CRISPR system does not always work do to anti-CRSPR proteins that inhibit the complex from working properly.
According to an article on ScienceDaily, researchers have finally discovered how these anti-CRISPR proteins work! Research done by biologist Gabriel C. Lander from the Scripps Research Institute, discovered that anti-CRISPR proteins work by inhibiting CRISPR’s ability to identify and attack viral genomes. Just like there are different CRISPR systems, there are multiple anti-CRISPR proteins as well. One in particular mimics DNA to throw the CRISPR-guided detection machine off its course. Scientists have been able to further discover certain aspects of CRISPR and anti-CRISPR systems by using a high-resolution imaging technique called cryo-electron microscopy. They have discovered that the CRISPR surveillance complex analyzes a virus’s genetic material to see where it should attack by having proteins within the complex wrap around the CRISPR RNA, exposing specific sections of bacterial RNA. These sections of RNA then scan viral DNA, looking for genetic sequences they recognize. Lander describes these proteins as being very clever because they “have evolved to target a crucial piece of the CRISPR machinery. If bacteria were to mutate this machinery to avoid viral attacks, the CRISPR system would cease to function.” Therefore, CRISPR systems cannot avoid anti-CRISPR proteins without completely chancing the mechanism used to recognize DNA. Another type anti-CRISPR protein works a bit differently. Based on its location and negative charge, this anti-CRISPR protein acts as a DNA mimic, fooling CRISPR into binding this immobilizing protein, rather than an invading viral DNA.
Can Anti-CRISPR Proteins be beneficial?
Researchers are saying that the understanding of how these anti-CRISPR proteins work are extremely important! According to an article on GEN, the discovery and understanding of anti-CRISPR proteins actually allows researchers to have greater control over gene-edits. In this article, Dr. Sontheimer, a professor in the RNA The RNA Therapeutics Institute at UMass Medical School, expressed how “CRISPR/Cas 9 is a good thing because it introduces specific chromosome breaks that can be exploited to create genome edits, but because chromosome breakage can be hazardous, it is possible to have too much of a good thing, or to have it go on for too long.” Anti-CRISPR proteins can be beneficial and work as an off switch for CRISPR, therefore advancing gene editing!