96pc of us may have CRISPR immunity, but there’s no need to panic just yet

31 Oct 2018

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New research has found that the much-hyped CRISPR gene-editing tool might not work for most humans, but there could be a fix in the works.

CRISPR-Cas9 – commonly just referred to as CRISPR – has been heralded as a potential answer to removing the faulty genetic code that leads to the development of hereditary conditions such as Huntington’s disease.

However, despite initial promise, testing in mice has shown its effects to have resulted, in some cases, in unintended, negative consequences in other parts of our DNA.

Now, according to Xconomy, a recent paper published in Nature Medicine has cast further doubt after it found that 96pc of people in a study had T-cell-based immunity against the Cas9 enzyme that ‘cuts’ the DNA.

The 48 volunteers were exposed to Cas9 derived from the bacterium Streptococcus pyogenes, one of the most commonly used enzymes with CRISPR. With a further 85pc of volunteers showing they had antibodies against it, these findings suggest that immunity to CRISPR’s effects is even greater than we thought. A previous study discussed earlier this year showed 65pc of participants had antibodies against it.

At that time, the team was unable to return a result to show whether there was T-cell-based immunity. This would be significantly damaging to CRISPR researchers, with the share price of a number of companies working with the technology already affected.

No need to panic

Speaking of the results, the lead researcher on the study, Michael Schmueck-Henneresse of Charité University Medicine Berlin, said his initial surprise gave way to a clear realisation.

“It made sense because the Streptococcus pyogenes bacterium is one of the most common causes for bacterial infections in humans and we have all been through multiple infections and potentially even been colonised by it,” he said. He added that there is no way to predict what will happen when human trials begin (expected within a year), but it could depend on how exactly is it delivered in the body.

Schmueck-Henneresse warned that those organising the trials should limit Cas9’s activity in cells, and suggested that an immunosuppressive drug should be administered beforehand.

But before we start thinking CRISPR’s potential is over before it even begins, Australian-based genome-editing expert Gaetan Burgio and other researchers claim to have found a way to circumvent the immunity by modifying the Cas9 protein or Cas9 orthologs.

It is also possible that another form of DNA-cutting enzyme might do the trick, derived from bacteria with no record of infecting humans.

Colm Gorey was a senior journalist with Silicon Republic