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CRISPR upgrade harnesses 'jumping genes'

10 June 2019
Appeared in BioNews 1001

Adapting CRISPR-mediated genome editing to make use of 'jumping genes' could improve scientists' ability to insert DNA into the genome

Deleting sections of DNA from the genome is relatively easy, but replacing a section of DNA with another sequence is much more difficult. The latter could be extremely useful in treating certain genetic diseases, replacing a section of DNA containing a disease-causing mutation with a 'corrected' DNA sequence. 

'It's still in the experimental phase,' geneticist Dr Helen O'Neill of University College London, who was not involved in the research, told the New Scientist. 'But it's quite exciting.'

Professor Feng Zhang and his team at the Massachusetts Institute of Technology appear to have developed a way to do just that, in bacteria, using 'jumping genes', with a success rate vastly higher than with conventional CRISPR. These genes are thought to be genomic parasites, inserting themselves in different places around the genome with the help of enzymes called transposases.

A sub-group of transposons make use of CRISPR – naturally present in bacteria as part of their immune system – in their travels around the genome. These transposons use an enzyme called Cas12k to find specific DNA sequences, and a transposase inserts the jumping gene into the DNA at that site. 

Professor Zhang's team used Cas12k and one of this group of transposons – called Tn7 – to insert a DNA sequence into the Escherichia coli genome at a target site, with an 80 percent success rate. Conventional CRISPR-Cas9 has about a 1 percent success rate for DNA insertion. 

Researchers have greeted the results as 'remarkable'. The next stages are to see if the same can be replicated in more complex model organisms and eventually humans. One potential drawback was off-target effects, which happened at a rate of around one in 100 edits. 

'I think it's something that could be used therapeutically,' Professor Shoukhrat Mitalipov of Oregon Health and Science University, who was not involved in the study, told STAT News. 'It's only a first step, but it's really encouraging.'

The research was published in the journal Science

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