How bacteria invented gene editing

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Source: BBC

This week the UK Human Fertilisation and Embryology Authority okayed a proposal to modify human embryos through gene editing. The research, which will be carried out at the Francis Crick Institute in London, should improve our understanding of human development.

It will also undoubtedly attract controversy – particularly with claims that manipulating embryonic genomes is a first step towards designer babies. Those concerns shouldn’t be ignored. After all, gene editing of the kind that will soon be undertaken at the Francis Crick Institute doesn’t occur naturally in humans or other animals.

It’s relatively fast, cheap and easy to edit genes with CRISPR

It is, however, a lot more common in nature than you might think, and it’s been going on for a surprisingly long time – revelations that have challenged what biologists thought they knew about the way evolution works.

We’re talking here about one particular gene editing technique called CRISPR-Cas, or just CRISPR. It’s relatively fast, cheap and easy to edit genes with CRISPR – factors that explain why the technique has exploded in popularity in the last few years.

But CRISPR wasn’t dreamed up from scratch in a laboratory. This gene editing tool actually evolved in single-celled microbes.

UK scientists are now allowed to genetically modify human embryos (Credit: SPL)

UK scientists are now allowed to genetically modify human embryos (Credit: SPL)

CRISPR went unnoticed by biologists for decades. It was only at the tail end of the 1980s that researchers studyingEscherichia coli noticed that there were some odd repetitive sequences at the end of one of the bacterial genes. Later, these sequences would be named Clustered Regularly Interspaced Short Palindromic Repeats – CRISPRs.

For several years the significance of these CRISPRs was a mystery, even when researchers noticed that they were always separated from one another by equally odd ‘spacer’ gene sequences.

Microbes can deliberately edit their own genomes

Then, a little over a decade ago, scientists made an important discovery. Those ‘spacer’ sequences look odd because they aren’t bacterial in origin. Many are actually snippets of DNA from viruses that are known to attack bacteria. In 2005, three research groups independently reached the same conclusion: CRISPR and its associated genetic sequences were acting as a bacterial immune system.

In simple terms, this is how it works. A bacterial cell generates special proteins from genes associated with the CRISPR repeats (these are called CRISPR associated – Cas – proteins). If a virus invades the cell, these Cas proteins bind to the viral DNA and help cut out a chunk. Then, that chunk of viral DNA gets carried back to the bacterial cell’s genome where it is inserted – becoming a spacer. From now on, the bacterial cell can use the spacer to recognise that particular virus and attack it more effectively.

Gene editing also occurs in nature (Credit: SPL)

Gene editing also occurs in nature (Credit: SPL)

These findings were a revelation. Geneticists quickly realised that the CRISPR system effectively involves microbes deliberately editing their own genomes – suggesting the system could form the basis of a brand new type of genetic engineering technology. They worked out the mechanics of the CRISPR system and got it working in their lab experiments. It was a breakthrough that paved the way for this week’s announcement by the HFEA.

Exactly who took the key steps to turn CRISPR into a useful genetic tool is, however, the subject of a huge controversy. Perhaps that’s inevitable – credit for developing CRISPR gene editing will probably guarantee both scientific fame andfinancial wealth.

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