Biotechnology Genetics

New Anti-CRISPR Proteins May Hold the Key to Safe Genetic Editing!

Anti-CRISPR

Everything in this world has a weak point, nothing is immortal, and this fact applies to everything and everyone either if it’s an average Joe or a great hero like Achilles. The same is the case with this new gene-editing tool, so-called CRISPR Cas9. Until now, the methods were considered perfect and create breakers in different forms. Which is somehow essential to consider it in case of its misuse though.

CRISPR – a novel and versatile method of gene editing that could be used to edit the genome of almost any organism. Naturally, it is found in bacteria. Almost every bacterium uses this mechanism to grapple invading viruses usually bacteriophages, by stopping their DNA and chopping it with a specific scissor-like protein called Cas 9. Thus, it works as an adaptive immunity in bacteria.

Video: showing CRISPR editing DNA in real time

 

We already published articles regarding CRISPR potential and their applications both in humans and animals. Although the results scientists got by its use are worth appreciation; but what if this gene-editing tool is used by some mad scientists or an evil group to harm humanity? What if this CRISPR is used as a new bioweapon? What will be our strategy in such cases?

CRISPR co-inventor Jennifer Doudna said in her book; “A Crack In Creation,” that she itself is afraid of the misuse of the technique, “Could I and other concerned scientists save CRISPR from itself…before a cataclysm occurred”.

The US intelligence agencies already declared the “gene-editing as a potential weapon of mass destruction.” A program named “safe genes” initiated by DARPA pours a massive budget of $65 million to find techniques that could possibly reverse the effect the CRISPR.

In 2017, UC Berkeley, including Doudna, claimed a  big part of the DARPA contract.

 

DARPA Anti CRISPR project
Defense Advanced Research Projects Agency announced $65 million in funding to seven projects around the country – including one led by UC Berkeley – to improve the safety and accuracy of gene editing. Image: UC Berkeley

Anti-CRISPR

Before Jennifer Doudna gets part of the DARPA project, many scientists already had significant clues for stopping CRISPR. – That’s the viruses considered gods of genetic variations. And they can tackle any therapeutic approach done to stop them; by changing their genetic makeup and making them Quasi-species.

Moreover, some viruses also evolved to develop their antidotes to cope with bacterial CRISPR. Scientists call this the “Anti-CRISPR.”

In 2013 first anti-CRISPR was discovered by a student named Joseph Bondy-Denomy at the University of Toronto. “It was serendipity. We stumbled onto the fact that some phages seem to be resistant to CRISPR. When we put the phage into a cell, the bacteria couldn’t protect itself,” says Bondy-Denomy.

The number of scientists working on anti-CRISPR is very less as compared to scientists working on CRISPR. Already more than 40 anti-CRISPR proteins have been identified.

anti crispr
This visual abstract depicts the finding that naturally occurring inhibitors of CRISPR-Cas9 can block genome editing in cultured human cells, providing a means to spatially, temporally, and conditionally control Cas9 activity. [Pawluk et al./Cell 2016]
Amit Choudary of Havard Medical School claimed that his team found two drugs that can stop CRISPR while working with human cells. Research believes that this anti-CRISPR will further improve the precision and accuracy of gene editing. For instance, a team of the researcher in Germany combined anti-CRISPR with its own CRISPR. It allows them to edit genes only in one specific organ without disturbing the genome integrity of other organs (as they did DNA changes in the liver cells, not neurons or another organ).

Another severe harm that can be caused by using gene-editing tools without their antidote is the extinction of organisms. Recently CRISPR was applied over some organisms including Bill & Melinda Gates Foundation-backed project using gene-editing tools in wild mosquitoes to tickle malaria. Others want to develop gene drive in mice and monkeys.

Explore More: Cloned Gene-Edited Monkeys with Horrifying Results

But what if all these gene drive experiments lead to the extinction of such species. In such cases, it is necessary to combine it with its antidote (anti-CRISPR). As a proof of concept, in 2018, scientists in Kansas engineered yeasts cells with anti-CRISPR that can resist any gene drive. “If some North Korean lab comes at you with a gene drive to wipe out an economically important crop, you could have a transgenic crop that [is resistant]. That is the drawing board scenario,” says Erik Sontheimer of the University of Massachusetts Medical School.

 

CRISPR Defense

As part of the DARPA project, groups of scientists, including Doudna Lab, initiate their experiments in mice to check whether the anti-CRISPR works or not.

One of them is a research team in Sandia National Laboratories that involved mice primed for gene-editing. The new mice born will be having Cas 9 protein in every cell.

Schoeniger, who leads this research, concluded that this would also help them find a new anti-CRISPR that will block the same process in mice. He believes that any accidental exposure to CRISPR can lead to harm.

He says, “And if I get a mutagen sprayed in my eyes, it would be nice to stop it.” In the meantime, he added, “learning how to stop CRISPR in its classic, simplest form, seems like a good place to start. It seems obvious that we would like to modulate the technique, so let’s do that while trying to sort out the priorities”.

He explained his inability to understanding and finding the actual result in such words; “to a certain extent, it is a mess; how this technology is exploding fast.

 

Explore more: The DARK Side of CRISPR

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