CRISPR 2.0? New modification overcomes collateral damage during editing

8 Dec 2017340 Views

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A team of researchers may have found a way to overcome the CRISPR gene-editing technology’s biggest flaw: its ability to damage other genes.

CRISPR-Cas9 is a technology that promises to usher in a new age of genetics, whereby harmful, hereditary genes can be ‘snipped’ out and replaced with healthy ones.

One of the most recent examples was conducted by a team that successfully removed and corrected the gene responsible for hypertrophic cardiomyopathy (sudden death syndrome).

The reason that such a promising technology has not gone mainstream is because its long-term effects remain unknown, with concerns that it could lead to hundreds of unintended mutations in surrounding genes.

But now, according to The Guardian, a team of researchers from the Salk Institute in California has created what some might see as ‘CRISPR 2.0’ because, instead of physically cutting out the DNA from genetic code, it “turns up the volume” on the affected area.

In a paper published to Cell, the team explained that in its new method, the Cas9 protein used to cut out the DNA now actually latches on to it, thanks to the inclusion of a third molecule that can seek out the target area.

The method was tested in mice with muscular dystrophy, a muscular degeneration disorder caused by a mutated gene that produces smaller amounts of protein called dystrophin, found in muscle fibres.

Rather than cutting out the bad gene, the new CRISPR method significantly boosts the power of another protein called utrophin, which helps to balance out the lack of dystrophin.

As no gene is removed, there should be a much lower chance of unwanted mutations occurring in the surrounding genes.

Turn back ageing?

“Cutting DNA opens the door to introducing new mutations,” said the study’s lead author, Juan Carlos Izpisua Belmonte.

“That is something that is going to stay with us with CRISPR or any other tool we develop that cuts DNA. It is a major bottleneck in the field of genetics – the possibility that the cell, after the DNA is cut, may introduce harmful mistakes.”

Belmonte has even gone as far as to say the treatment could reverse the ageing process, but this is very far down the line.

“Our goal will be to reactivate genes silenced by ageing, or to use the system to replenish stores of adult stem cells, which promote regeneration but are typically depleted with age,” he explained.

Reaction from other research groups has been understandably cautious, with Alena Pance, a senior scientist from the UK’s Wellcome Trust Sanger Institute, claiming that it could still cause side effects in untargeted genes.

If it were used on one particular organ, she said, it could affect the same genes across the body, leading to unwanted side effects.

Colm Gorey is a journalist with Siliconrepublic.com

editorial@siliconrepublic.com