Gene Editing That Spreads Within The Body Trialled For First Time

“Imagine if, instead of delivering a leaflet individually to each home, a postal worker just had to give one to a volunteer on each block, who then photocopied it and handed out copies to neighbours. That postal worker would get leaflets into dramatically more homes that way. Biologists are hoping a similar approach could make gene editing better at treating all kinds of conditions.

The idea is that each cell in the body that receives the initial delivery will make lots of copies of the gene-editing machinery and pass most of them on to its neighbours, amplifying the effect. This means that disease-correcting changes could be made to the DNA of more cells.”

And while that sounds great and all, personally, the biosecurity implications of this new method are potentially horrifying. But anyways …

“In tests in mice, Wayne Ngo at the University of California, Berkeley, and his colleagues – including CRISP-R gene-editing pioneer Jennifer Doudna – have managed to triple the number of liver cells that were edited using this approach.”

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“To test the idea, the team created a piece of DNA coding for the Cas9-viral proteins. When the DNA was injected under pressure into the livers of mice, it got into just 4 per cent of cells, but, overall, 12 per cent of the cells were gene edited.

For treating people, the gene-editing machinery would be delivered in other ways. The injection method was just used for proof of principle.

“It’s not particularly efficient, but it does show that our system makes a difference,” says Ngo. “Threefold amplification is a great place to start. I think it makes some of our current delivery systems good enough to treat some diseases. More could be better, and so we are actively exploring strategies to do that as well.””

“Besides greater efficiency, amplified gene editing could also allow lower doses to be used, which would make treatments safer.

Biologists have been exploring these vesicle-budding approaches for decades, says Gaetan Burgio at the Australian National University in Canberra, but Ngo’s team may be the first to demonstrate it working in animals for gene editing. However, Burgio says the researchers have more work to do to confirm their results.

“Proper controls and measures need to be performed to really demonstrate their claims,” he says.”

“There are already experimental self-amplifying mRNA vaccines, where mRNAs delivered to cells code for machinery that makes more copies of the vaccine mRNAs. The idea is to make mRNA vaccines safer and cheaper, because lower doses are needed. However, in this case, the extra mRNAs remain inside the cells where they are made.”

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How does the new amplified gene editing technique increase the number of edited cells? The new method functions like a neighborhood distribution network: instead of delivering gene-editing machinery to every individual cell, the initial delivery is made to a smaller group of cells that then photocopy the machinery and pass it on to their neighbors. In recent tests led by Wayne Ngo at the University of California, Berkeley, and Jennifer Doudna, this approach managed to triple the number of liver cells successfully edited in mice, increasing the overall coverage from an initial 4 percent delivery to 12 percent total gene editing. This amplification strategy not only improves efficiency but also potentially enhances patient safety by allowing doctors to use lower initial doses of gene-editing treatments.