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CRISPR

A technology that can be used to edit genes

CRISPR

CRISPR is a technology that can be used to edit genes and, as such, will likely change the world.

The essence of CRISPR is simple: it’s a way of finding a specific bit of DNA inside a cell. After that, the next step in CRISPR gene editing is usually to alter that piece of DNA. However, CRISPR has also been adapted to do other things too, such as turning genes on or off without altering their sequence.

There were ways to edit the genomes of some plants and animals before the CRISPR method was unveiled in 2012 but it took years and cost hundreds of thousands of dollars. CRISPR has made it cheap and easy.

CRISPR is already widely used for scientific research, and in the not too distant future many of the plants and animals in our farms, gardens or homes may have been altered with CRISPR. In fact, some people already are eating CRISPRed food.

CRISPR technology also has the potential to transform medicine, enabling us to not only treat but also prevent many diseases. We may even decide to use it to change the genomes of our children. An attempt to do this in China has been condemned as premature and unethical, but some think it could benefit children in the future.

CRISPR is being used for all kinds of other purposes too, from fingerprinting cells and logging what happens inside them to directing evolution and creating gene drives.

The key to CRISPR is the many flavours of “Cas” proteins found in bacteria, where they help defend against viruses. The Cas9 protein is the most widely used by scientists. This protein can easily be programmed to find and bind to almost any desired target sequence, simply by giving it a piece of RNA to guide it in its search.

When the CRISPR Cas9 protein is added to a cell along with a piece of guide RNA, the Cas9 protein hooks up with the guide RNA and then moves along the strands of DNA until it finds and binds to a 20-DNA-letter long sequence that matches part of the guide RNA sequence. That’s impressive, given that the DNA packed into each of our cells has six billion letters and is two metres long.

What happens next can vary. The standard Cas9 protein cuts the DNA at the target. When the cut is repaired, mutations are introduced that usually disable a gene. This is by far the most common use of CRISPR. It’s called genome editing – or gene editing – but usually the results are not as precise as that term implies.

CRISPR can also be used to make precise changes such as replacing faulty genes – true genome editing – but this is far more difficult.

Customised Cas proteins have been created that do not cut DNA or alter it in any way, but merely turn genes on or off: CRISPRa and CRISPRi respectively. Yet others, called base editors, change one letter of the DNA code to another.

So why do we call it CRISPR? Cas proteins are used by bacteria to destroy viral DNA. They add bits of viral DNA to their own genome to guide the Cas proteins, and the odd patterns of these bits of DNA are what gave CRISPR its name: clustered regularly interspaced short palindromic repeats. Michael Le Page