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Gene Editing Achieved in Bacteria Using Transposon, Without CRISPR "Cutting"

Accepted submission by takyon at 2019-06-11 02:32:09

'Jumping genes' could help CRISPR replace disease-causing DNA, study finds []

In a 2017 study [...] four biologists wrote [] [open, DOI: 10.1073/pnas.1709035114] [DX []] that "it has not escaped our notice" that a funny little "jumping gene" might be harnessed for precision genome editing, giving classic CRISPR a hand at something it struggles to do: insert a string of healthy DNA in place of a disease-causing sequence, which for some genetic diseases might be the only path to a true cure.

The lead author of that study has been trying ever since to repurpose the jumping gene, but he (and other labs) was beaten to the punch on Thursday by CRISPR pioneer Feng Zhang of MIT and the Broad Institute. In a paper [] [DOI: 10.1126/science.aax9181] [DX []] in Science that zoomed from submission to acceptance in just 25 days (four months is more usual), Zhang and his colleagues describe turning a jumping gene — aka a transposon, or mobile genetic element — into a mini TaskRabbit gig worker: With an assist from CRISPR enzymes, it zips over to the part of the genome whose address it is given and delivers a package of DNA, pronto.

Zhang's team did all this in lowly bacteria, but other genome-editing biologists said the system could very well work in human cells, too, especially for repairing a disease-causing gene. "I think it's something that could be used therapeutically," said reproductive biologist Shoukhrat Mitalipov of Oregon Health and Science University, who was the first scientist in the U.S. to use CRISPR in human embryos. (He didn't create pregnancies with them.) "It could even be very important" for treating disease via genome editing, he added, because "it seems more efficient and precise [than classic CRISPR]. It's only a first step, but it's really encouraging."

This particular transposon, called Tn7, was discovered decades ago in bacteria. In general, transposons are pieces of DNA that sit within a genome, but for reasons that are somewhat mysterious have the ability to cut themselves out of their original site and jump to another. Tn7 uses the CRISPR enzyme Cas12 to lead it to its next home. Rather than cutting DNA, as Cas12 usually does, when paired with Tn7 it keeps its molecular scissors sheathed. Ever since the "it has not escaped our notice" hint in the 2017 paper, scientists have been looking for ways to control where the jumping gene jumps to. Constructing a new guide molecule should allow scientists to control where the DNA inserts itself in the genome.

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