Gene-Editing Technique CRISPR-Cas9 May Be Causing Hundreds Of Genetic Mutations

CRISPR may be causing hundreds of off-target mutations in the genome. Christoph Burgstedt/Shutterstock

The gene-editing technique CRISPR Cas-9, hailed as a major breakthrough for genetic modifications, may be introducing hundreds of previously unknown mutations into the DNA. A small study has found that the new method may cause mutations in off-target regions, but it's still too early to know if this is a common occurrence or an anomaly.

Hailed as one of the biggest advancement in genetics in recent times, CRISPR is an amazingly powerful tool that is now used across much of the field, and is even being trialled in humans in China. It has risen to such popularity due to its ability to quickly and easily identify the region of the genome that's to be altered and then precisely cut or insert other bits of DNA at this point.

When testing to see whether CRISPR is having any unwanted effects on other regions of the DNA, previous researchers didn't actually scour the entire genome. They used a computer model that predicted where the mutations may occur and then checked these areas to see if there was any unintended changes to the genetic code. By doing this, the scientists found that CRISPR seemingly causes little to no unwanted mutations, one of the reasons it gained so much popularity.

But a team of scientists from Columbia University Medical Center wanted to see if this held true across all of the genome. They took two mice that had CRISPR used on them and sequenced their entire genome, before comparing it to a mouse used as a control. The use of CRISPR had successfully cured the rodents of blindness, but it had also altered other parts of the genome.

The researchers found over 1,500 single-nucleotide mutations, in which just one base pair (either ATCG) had been changed, and over 100 more significant mutations involving either deletions or insertions. It is important to stress here that mutations to our genome are an ongoing process, and no side effects were reported in the mice from the study, but it is still of some concern.

The study was very small – involving just two gene-edited animals and one control – so the results could be down to a number of things, including the way in which CRISPR was actually used on them. Further experiments would need to be done in order to test whether or not the issue is more widespread than previously thought. 

Either way, the researchers don’t think that people should stop using the technique. “We're still upbeat about CRISPR,” explains study author Dr Vinit Mahajan in a statement. “We're physicians, and we know that every new therapy has some potential side effects – but we need to be aware of what they are.”

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