For years, scientists have used a tool akin to a pair of scissors for the complex task of gene-editing, but a newly discovered technique using “jumping genes” could offer a seamless, safer alternative.
Gene-editing is the process of altering a part of DNA — the code that governs much about how an organism develops and behaves. 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 defence system in bacteria — to locate a target in the 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.
But the process is not always effective — sometimes the repairs are incomplete, or incorrect, and the damage response prompted by the cutting can have negative side effects. Last year, a study found the technique was “frequently” causing “extensive” unintended gene mutations.
But new research published on Thursday in the journal Nature offers a totally novel way to edit genes in DNA: “jumping genes”, also known as transposons, can effectively slide into the DNA without cuts.
‘Incredible precision’ -
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, in the past scientists struggled with their tendency to land “just about anywhere in the genome, without rhyme or reason,” said Sternberg.
But they found that the jumping gene could effectively be programmed with a guide “so it can insert itself with incredible precision into user-defined sites in the genome”.
That means scientists can ensure 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 the additions were inserted precisely with no extra copies created elsewhere — a problem that can occur with CRISPR gene-editing.
The study was published just days after another US team presented similar work in the journal Science, which reportedly offers more efficiency than Sternberg’s technique, but less precision. — AFP
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