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Scientists have broken a new frontier in the rapidly evolving field of gene editing with the discovery of a way to program the recombination and rearrangement of DNA.
The new technique promises to expand the capabilities of existing methods such as Crispr gene editing, which is boosting research in areas from cancer prevention to reducing methane emissions from cows.
The so-called bridge RNA method, devised by researchers at the Californian nonprofit Arc Institute, could enable more precise modifications of the genetic code and avoid the need to break sequences and repair them later.
The RNA bridge system was a “novel mechanism for biological programming” that could act as a “word processor for the living genome,” said Patrick Hsu, an Arc Institute core scientist 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 fuels the drive by researchers and companies to develop advanced re-engineering techniques that can limit organisms’ genetic risks of developing diseases or other unwanted conditions.
The technique, which was published in an article in Nature on Wednesday, uses RNA or ribonucleic acid, a crucial carrier of biological information in living cells. Instructions in the RNA cause enzymes – or biological catalysts – known as recombinases, to carry out the genetic editing.
Emmanuelle Charpentier and Jennifer Doudna, developers of the Crispr-Cas9 “genetic scissors” technique, won the 2020 Nobel Prize in Chemistry. Last year, a gene-editing therapy targeting the blood disorders sickle cell disease and beta-thalassemia became the world’s first Crispr treatment to receive regulatory approval.
The promising sector needs heavy investment to help the technology cover a range of medical therapies and make them accessible to everyone, Doudna told the FT this year.
The latest development of RNA bridge technology is an “exciting advance in large-scale genome modification, with tantalizing potential for many applications,” according to a commentary also published in Nature by scientists not involved in the work.
The innovation raised the prospect of further developments of “powerful biotechnology tools,” according to 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, had yet to be tested for applicability to mammals, including humans, they added. Researchers would further need to ensure that the technique worked in large genomes where targeted genetic sequences may appear more than once, increasing the risk of unwanted edits.
The new technology could “substantially extend the reach of gene editing operations,” says Prof. Jason Chin, program leader at the UK Medical Research Council Laboratory of Molecular Biology.
“These new recombinases allow the user to program the DNA sequences on which these operations take place, providing much more flexibility,” says Chin, who was not involved in the study. It seemed “likely” that some version of the technology would be applicable to human cells, he added.
The Arc Institute was founded in 2021 to develop computational technology tools that have the potential to tackle complex diseases. It collaborates with Stanford University, University of California, San Francisco and UC Berkeley. The backers include Patrick Collison, CEO of payments company Stripe.