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Scientists have opened a new frontier in the fast-evolving field of gene editing with the discovery of a way to programme the recombination and rearrangement of DNA.
The novel technique promises to expand on the possibilities of existing methods such as Crispr gene editing, which is driving research in areas from cancer prevention to cutting cows’ methane emissions.
The so-called bridge RNA method devised by researchers at California’s non-profit Arc Institute could enable more precise modifications of genetic code and avoid the need to break sequences and later repair them.
The RNA bridge system was a “new mechanism for biological programming” that could act as a “word processor for the living genome”, said Patrick Hsu, an Arc Institute core investigator and assistant professor of bioengineering at UC Berkeley. “Bridge recombination can universally modify genetic material through sequence-specific insertion, excision, inversion and more,” he said.
The discovery boosts the push from researchers and companies to develop sophisticated re-engineering techniques that can curb organisms’ genetic risks of developing diseases or other undesirable conditions.
The technique, reported in a paper in Nature on Wednesday, uses RNA or ribonucleic acid, a crucial carrier of biological information in living cells. Instructions contained in the RNA direct enzymes — or biological catalysts — known as recombinases to carry out the genetic edit.
Emmanuelle Charpentier and Jennifer Doudna. developers of the Crispr-Cas9 “genetic scissors” technique, won the Nobel chemistry prize in 2020. Last year, a gene editing therapy to target the blood disorders sickle cell disease and beta thalassaemia became the world’s first Crispr treatment to win regulatory approval.
The promising sector needs heavy investment to help the technology cover a range of medical therapies and make it accessible to all, Doudna told the FT this year.
The latest development of RNA bridge technology is an “exciting advance for the field of large-scale genome modification, with tantalising potential for many applications”, according to a commentary also published in Nature, by scientists who were not involved in the work.
The innovation raised the prospect of further developments of “powerful biotechnological tools”, said the piece by Connor Tou and Benjamin Kleinstiver, of the Center for Genomic Medicine at Massachusetts General Hospital.
The RNA bridge approach, which has been used in bacteria, still needed to be tested for its applicability to mammals, including humans, they added. Researchers would further need to ensure the technique worked in large genomes in which targeted genetic sequences might occur more than once — raising the risk of unwanted edits.
The novel technology might “substantially increase the range of gene editing operations”, said Prof Jason Chin, a programme leader at the UK Medical Research Council Laboratory of Molecular Biology.
“These new recombinases allow the user to programme the DNA sequences at which these operations take place, which provides much more flexibility,” said Chin, who was not involved in the research. It seemed “likely” a version of the technology would be applicable to human cells, he added.
The Arc Institute was founded in 2021 to develop computational technological tools that have the potential to tackle complex diseases. It works with Stanford University, University of California, San Francisco and UC Berkeley. Its funders include Patrick Collison, chief executive of payments company Stripe.
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