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IThis is the phrase of choice for biologists who know more than they say. Since James Watson and Francis Crick finished their 1953 double-helix article by saying timidly that "we have not escaped our attention," this discovery could explain the role played by DNA as a molecule of heredity. Other scientists have slipped this clause into papers to be just as prescient.
In a study conducted in 2017, for example, four biologists wrote that "it did not escape our attention" that a funny "little gene jumper" could be exploited for the # 39, editing precision genomes, which would lend a hand to the classic CRISPR: healthy DNA chain instead of a disease-causing sequence, which could, for some genetic diseases, be the only way to heal truly.
The lead author of this study has been trying to reuse the jumper gene ever since, but he (and other labs) was beaten Thursday by CRISPR pioneer Feng Zhang of the Broad Institute. In a Science article that went from submission to acceptance in just 25 days (four months is more common), Zhang and her colleagues describe the transformation of a jumping gene – aka a transposon or mobile genetic element – into a mini TaskRabbit concert organizer: With a CRISPR Enzyme help, it zips over the part of the genome it's address to and provides a package of DNA, pronto.
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Zhang's team did all this with small bacteria, but other genome-modifying biologists said the system could work well in human cells, including repairing a gene responsible for the disease. "I think this is something that could be used for therapeutic purposes," said reproductive biologist Shoukhrat Mitalipov of the University of Oregon Health and Science, the first scientist in the United States to use CRISPR in human embryos. (He did not create a pregnancy with them.) "It could even be very important" for the treatment of the disease via genome modification, he added, because "it seems more efficient and more accurate [than classic CRISPR]. This is only a first step, but it is really encouraging.
This transposon, called Tn7, was discovered in bacteria decades ago. In general, transposons are fragments of DNA in a genome, but for some mysterious reasons, they have the opportunity to cut themselves off from their original site and jump to another.
Tn7 uses the CRISPR Cas12 enzyme to carry it home. Rather than cutting DNA, as Cas12 usually does, when it is associated with Tn7, it keeps its molecular sheaths sheathed. Since the mention "this has not escaped our attention" in the 2017 paper, scientists have been looking for ways to control the passage of the gene jumper. The construction of a new guide molecule should allow scientists to control where the DNA inserts into the genome.
This is essentially what Zhang's team accomplished. Starting with Tn7 from Scytonema hofmanni bacteria, they created new guide molecules to drive it to a specific address in the genomes of E. coli and insert its DNA packet. Compared to the ordinary CRISPR 1% DNA insertion success rate, the jumping gene system scored about 80%.
Crucially, the insertion did not require cutting the genome into slices. Such "double-stranded DNA breaks" often trigger genomic havoc, with entire pieces of chromosomes being lifted and deposited in new DNA neighborhoods – which in pre-CRISPR gene therapy caused cancer in some patients. Any genome editing technology that avoids double-strand breaks may therefore have a security advantage.
"As a feasibility study, she is doing an excellent job in showing the potential of these systems and should be a very important document," said Cornell University microbiologist Joseph Peters, lead author of the paper. 2017 which predicts that transposons could be part of the CRISPR toolkit. "At this point, it is not entirely clear if this specific system will be useful for genome modification," because some features of Tn7 might limit its effectiveness in organisms other than bacteria, but in general, Tn7 " is very exciting in itself. potential genome editor. "
Zhang calls the system "transposase associated with CRISPR" or CAST. He and one of his co-authors, Jonathan Strecker, have filed a patent for this product.
The jumping gene version of CRISPR is probably better than the classic version when curing a genetic disease requires running a gene normally by replacing its misspelled "letters" of DNA. The CRISPR tries to do it by removing the mutation (like Word Fi of orthografi) and proposing the correct letters (phy). Unfortunately, DNA is also reluctant to accept and accept the substitution that an infant must open to peas.
CAST does not seem to have any problem inserting DNA. When scientists programmed it for 48 targets in the E genome. Coli, the CAST hit 29. (In general, the CRISPR guides do not work all the time.) He produced the desired edition, inserting DNA, in 80% of the bacteria, a rate that leaves the CRISPR classic in the dust.
One of the red flags was that CAST had inserted DNA in places where it was not supposed, an "untargeted" problem that also poisons the classic CRISPR. The 99: 1 ratio of target changes to non-target targets seems high, but further research will be needed to demonstrate whether a single change in non-targeted DNA is enough to destroy, for example, an essential tumor suppressor gene. .
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