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What is CRISPR-Cas?

CRISPR-Cas is a powerful new technology that is revolutionising biology. It's like cut and paste for DNA.
CRISPR cas is a powerful new technology that is revolutionising biology. It’s like cut and paste for DNA. Using CRISPR cas, or CRISPR for short, scientists can delete, tweak, or completely replace the genes of any organism. And they can do it more cheaply, easily, and efficiently than ever before. Researchers are already trying to use CRISPR to introduce genes for disease resistance into wheat, insert malaria-blocking genes into mosquitoes, and remove HIV genes from infected cells in humans. Scientists didn’t design CRISPR themselves. Instead they borrowed it from microbes, like bacteria and archaea. These microorganisms use the CRISPR system as a defense mechanism against invading parasites like viruses.
It works like this: when a virus attacks a bacterium, it introduces its own DNA into the cell. DNA contains the instructions for life. It’s made up of four different chemical units, which the cell reads like a code. Some viruses use their DNA to hijack the bacterium’s cellular machinery and make more copies of themselves. They eventually burst out of the cell and spread to other bacteria. But with CRISPR cas, the bacterium can fight back. The ‘cas’ part of CRISPR cas is an enzyme that works like molecular scissors. The bacterium uses cas to cut the invading DNA into two, disabling the virus. Next, the bacterium inserts a section of the intruder viral-DNA into a special area of its own genome.
Over time the bacterium uses this area to build up a library of ‘bad guys’. It forms a kind of parasite ‘hit list’, so that it can recognise them if they attack again in the future. The bacterium copies these sequences into related molecules called RNA. Each RNA guide is combined with a cas enzyme, turning the molecular scissors into precise targeted weapons. Now, when they encounter a piece of DNA inside the cell that matches the sequence in the guide, cas will snip the intruder DNA and disable it. Before we discovered CRISPR, we thought that the immune systems of bacteria were simple crude tools that worked for everything. But now we know their defences are much more sophisticated.
CRISPR cas forms what’s known as an adaptive immune system, much like our own. With it, the bacteria can form immune memories of invaders and respond more quickly and precisely, if they attack in the future. Once they figured out what CRISPR was, and how it worked, scientists realised they could take it out of microbes and use it as a gene-editing tool in any organism. You take a cas enzyme and provide your own RNA guide-molecule, which matches the genetic sequence of the gene you want to edit. If you introduce this into a cell, cas will then snip the host’s genome in precisely the place you specify. This ends up disabling the gene.
Scientists have even worked out how to get the cell to stitch a new gene into the place of the cut one. Scientists can do these things already with other tools but CRISPR just makes things easier, quicker, and much more accessible. At its most basic level, CRISPR allows scientists to study individual genes by seeing what happens when you turn them off. But using CRISPR to accurately edit the genomes of plants, microbes, animals and humans opens up almost endless possibilities. Selectively killing antibiotic-resistant bacteria, engineering the body’s cells to fight cancer, even editing pig genes so that we can use their organs for human transplants. The precise nature of CRISPR means we could even use it to eliminate certain genetic diseases in humans.
These kinds of applications are still some way off. Even though CRISPR is powerful, it can still make mistakes, sometimes missing its targets, or making unwanted edits. And there are ethical concerns about what should and shouldn’t be allowed with this kind of technology, especially when it comes to modifying the human genome. CRISPR has come a long way since its origins in tiny microbes but it really does have the potential to change the world. The CRISPR revolution is well and truly here. And it’s only just beginning.

CRISPR-Cas is a powerful new technology that is revolutionising biology. It’s like cut and paste for DNA and provides efficient and accurate processes for editing genomes.

Scientists are already using CRISPR to introduce genes for disease resistance into wheat and insert malaria-blocking genes into mosquitoes. CRISPR could even allow us to eliminate certain genetic diseases in humans.

These types of experiments raise important ethical issues, which will be discussed further in the next step.

The associated video was produced by the Microbiology Society. Further information can be found at the society’s website.

Note that, as we already highlighted at the end of week 2 of this course, this research was rewarded in October 2020 with the Nobel Prize in Chemistry. The award was made to Emmanuelle Charpentier and Jennifer A. Doudna “for the development of a method for genome editing”. Further details are available here.

© UEA and Biochemical Society, 2020. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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Biochemistry: the Molecules of Life

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