CRISPR Cas9 genome editing explained | WIRED UK – Wired.co.uk

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Targeted, genetic modification in humans is no longer in the realm of science fiction. Both the UK and US governments have approved the use of a cheap and accurate DNA-editing technique called CRISPR-Cas9 in human embryos and adults. The technique allows scientists to edit genes with unprecedented precision, efficiency, and flexibility but how does it work and why is it so controversial?

CRISPR, pronounced 'crisper', stands for Clustered Regularly Interspaced Short Palindromic Repeat. The name refers to the way short, repeated DNA sequences in the genomes of bacteria and other microorganisms are organised.

CRISPR was inspired by these organisms defence mechanisms. Bacteria defend themselves from viral attacks by stealing strips of the invading virus DNA, which they splice in their own using an enzyme called Cas. These newly-formed sequences are known as CRISPR. The bacteria make RNA copies of these sequences, which help recognise virus DNA and prevent future invasions.

In 2012, scientists turned CRISPR from a bacterial shield into a gene-editing tool.

They replaced the bacterial CRISPR RNA system with a modified guide RNA. This RNA acts as a kind of wanted poster - it tells a bounty hunter enzyme called CAS9 where to look. The enzyme scans the cell's genome to find a DNA match then slices for the DNA in the cells enzymes. To repair damage at that point, scientists can change or add DNA within the cell.

By feeding CAS9 the right sequence or guide RNA, scientists can cut and paste parts of the DNA sequence, up to 20 bases long, into the genome at any point.

The technique is significant because it gives genetic biologists a powerful tool for gene editing. More importantly, it's cheap. The major impact of CRISPR has been in developing new model systems, cells and animals, that are more rapid to develop and much more accurate than previous genetic models, Dr Ed Wild, from UCL Institute of Neurology, told WIRED.

It gives rise to a huge range of opportunities. Plans are underway to edit allergens in peanuts, create mushrooms that don't brown and breed genetically-engineered mosquitoes that cannot transmit malaria. There is even a project to bring back the woolly mammoth from extinction.

But it doesn't stop there. CRISPR is already being used to edit pig DNA so their organs can be transplanted into humans; China is using CRISPR-edited cells in living humans, to inject cancer-fighting white blood cells into a patient. The technique could also be used to target illnesses such as system fibrosis, sickle-cell anaemia and Huntington's disease.

However, there is a long road ahead. Editing the genomes of embryos is much easier in principle, but many genetic conditions dont require it because a proportion of embryos are naturally free from the mutation already, Dr Wild added.

For example, 50 per cent of embryos from a parent with Huntingtons disease, and 25 per cent of embryos from a couple carrying the mutation that causes cystic fibrosis, would be free from harmful mutations without any need for genome editing.

There are many challenges with viral delivery and concerns about side-effects from turning cells into CRISPR factories, too. The proteins being introduced came from bacteria, so they could trigger the immune system. There are also concerns about the fact it may be impossible to turn them off.

These seem like solvable problems but we know that it will take many years to solve them, Dr Wild told WIRED. In the short term CRISPR will be used to study disease in much more efficient and targeted ways, for example by developing new model systems or by simulating the effect of treatments using genetic editing, Dr Wild says.

In the medium term, it may be used to produce cleaner versions of existing therapeutics, like therapeutic stem cells edited to be closer to the tissue type they are trying to replace.

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CRISPR Cas9 genome editing explained | WIRED UK - Wired.co.uk