For years, scientists have used a tool akin to a pair of scissors for the complex task of gene editing, but a new technique using “jumping genes” could offer a seamless, safer alternative.
Gene editing is the process of altering a part of DNA. It can correct or delete parts of that code, or insert sections for reasons that include preventing disease.
A key tool for editing is the CRISPR-Cas9 process, which uses CRISPRs — a part of the immune defense system in bacteria — to locate a target in DNA, and the protein Cas9 to “snip” the DNA strand.
The DNA then repairs itself, sometimes guided by a template that is inserted during the editing process.
However, the process is not always effective — sometimes the repairs are incomplete or incorrect, and the damage response prompted by the cutting could have negative side effects.
However, research published yesterday in the journal Nature offers a novel way to edit genes in DNA: “Jumping genes,” also known as transposons, can slide into the DNA without cuts.
The jumping gene “possesses all the necessary chemical properties to directly insert, or integrate ... without a DNA double-strand break,” lead author Samuel Sternberg said.
“You essentially sidestep all that complexity and you obviate the need for a DNA break,” added Sternberg, an assistant professor at Columbia University’s Department of Biochemistry and Molecular Biophysics.
The research was inspired by the discovery in 2017 that some types of jumping genes contain the CRISPR-Cas9 system.
Sternberg and his team decided to focus on the jumping gene in the bacterium Vibrio cholerae and see whether it could be used for editing.
While the properties of jumping genes have been known for some time, scientists have struggled with their tendency to land “just about anywhere in the genome, without rhyme or reason,” Sternberg said.
However, they found that the jumping gene could be programmed with a guide “so it can insert itself with incredible precision into user-defined sites in the genome.”
That means scientists could ensure that the edits are made in the correct place and the correct way, and frees them from relying on the DNA’s own repair mechanism.
The researchers found the jumping gene was capable of depositing “genetic cargoes into the genome,” delivering sequences up to 10,000 bases long.
Researchers checked their work by sequencing the edited genome and found that the additions were inserted precisely with no extra copies created elsewhere.
The study was published just days after another US team presented similar work in the journal Science.
The new technique holds “really exciting” potential — including for treating people, Sternberg said.
“This approach could allow for therapeutic genes to be inserted into the genome in a potentially safer way than is currently possible,” he said.
It could also be a game-changer for certain types of cells, such as neurons, which resist gene editing using the “cutting” process.
The technique might also open up new editing options in industrial biotechnology and complex bacterial communities, such as those in the gut, Sternberg said.
While the research offers a new tool for gene editing, it does not change the debate about germline editing, Sternberg added.
“The issue, at least right now, isn’t really the way that a change is made, but whether to make the change in the first place,” he said.
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