Powerful CRISPR upgrade uses 'jumping genes' to directly insert DNA
Updated: Mar 6, 2020
The CRISPR genome editing technology currently revolutionising biology may soon become even powerful. A new variant of the method based on “jumping genes” could make it much easier to insert pieces of DNA into genomes.
“It’s still in the experimental phase,” says geneticist Helen O’Neill of University College London. “But it’s quite exciting.”
Biologists would love to edit genomes with the same ease we can change digital texts using the “find and replace” command. What CRISPR currently excels at, however, is “find and delete”.
The standard form of CRISPR involves adding a protein called Cas9 to a cell along with a piece of guide RNA. The protein searches through the genome until it finds DNA that matches the guide RNA sequence and then cuts the DNA at this point. Some DNA is lost when the cell sticks the ends back together, resulting in deletions that typically disable genes.
But in many cases it would be better to fix faulty genes rather than disable them. It is possible to do this by adding a corrected gene to a cell along with the CRISPR Cas9 protein and the RNA guide. Cells sometimes splice the corrected version into the genome when they repair the DNA.
Unfortunately, this typically works only 20 per cent of the time, and in many cell types it simply doesn’t work at all.
Lots of teams are working on improving the “find and replace” function. Feng Zhang of the Massachusetts Institute of Technology has now developed a whole new approach based on transposons, also known as jumping genes.
These extremely selfish genes do nothing but copy and paste themselves from one part of the genome to another using enzymes called transposases. These genetic parasites are extremely common: more than half of our genome consists of now defunct jumping genes.
It was recently discovered that a few jumping genes have hijacked the CRISPR systems that bacteria use to defend against viruses. These Tn-7 jumping genes use a protein called Cas12k to find specific sequences. But these variants don’t cut the DNA at the target sequence; instead transposase enzymes insert the jumping genes into this site.
Read more: What is CRISPR?
Feng’s team have now shown the Cas12k protein and the Tn-7 transposes can be used to insert pieces of DNA several thousand letters long into specific sites in the genome of the E. coli bacterium. What’s more, it worked around 80 per cent of the time.
“Overall, the results shown in the paper are remarkable,” says Gaeten Burgio of the Australian National University, who studies CRISPR systems. But the team have yet to show this approach works in animal and plant cells, he cautions.
If this jumping gene CRISPR system can be made to work in complex cells, it would give biologists “find and add” function. That’s not the “find and replace” function of their dreams but it would be a powerful addition to our toolset that would be useful for everything from basic research to treating diseases.
Journal reference: Science, DOI: 10.1126/science.aax9181