Breakthrough Gene-Editing Tool is Better Than CRISPR

New ‘prime editing’ technology could correct 89% of genetic defects

New ‘prime editing’ technology could correct 89% of genetic defects

But the researchers say that they won't be completely eschewing other methods in favor of prime editing.

Scientists in the U.S. have developed a powerful new genome editing system that could offer significantly more precision and efficiency than the current CRISPR standard.

The new technique is called "prime editing", and was developed by researchers from the Broad Institute of MIT and Harvard, who published their findings Monday in the journal Nature. The fix system is however unreliable and can insert or delete DNA letters at the points where the genome was cut, leading to an uncontrollable mixture of edits that vary between cells. The most common approach, known as Crispr-Cas9, has been likened to "molecular scissors" which home in on a particular DNA sequence and then cut it in two.

In addition, the new method doesn't cut both strands of the DNA double helix, minimizing the chances of making unintended changes that could be risky, Liu says.

As powerful as that system is, it isn't without its risks.

Nicholas Katsanis, who studies genetic medicine at the Children's Hospital of Chicago, says that "there's no denying that there's some off-target effect [with CRISPR-Cas9] but the fear of the off-target effects is more than the reality".

I'm sure we've all heard of Crispr specifically Crispr-Cas9, developed 7 years ago, which scans the DNA and then makes a cut like a microscopic pair of scissors, which gives the ability to edit the DNA.

First, the pegRNA guides the prime editor to the desired section of the genome. The pegRNA also contains a sequence of letters that will be inserted into the genome - the RT protein reads that sequence and writes the corresponding DNA letters to the end of the nicked piece of DNA.

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The researchers further report a variety of successful edit types in human cells and primary mouse neurons, including all 12 possible ways to replace one DNA letter with another, insertions of new DNA segments up to 44 DNA letters long, precise deletions of up to 80 DNA letters, and modifications combining these different types of edits.

"You can think of prime editors as being like word processors capable of searching for target DNA sequences and precisely replacing them with edited DNA sequences", Liu said.

Out of the 75,000 different mutations that can cause disease in people, 89% of them can be fixed by Prime Editing says Dr. David Liu, a researcher working on the project.

"We're not aware of another editing technology in mammalian cells that offers this level of versatility and precision with so few byproducts".

"With prime editing, we can now directly correct the sickle-cell anemia mutation back to the normal sequence and remove the four extra DNA bases that cause Tay-Sachs disease, without cutting DNA entirely or needing DNA templates", according to Liu, a professor of chemistry and chemical biology at Harvard.

Liu says his team has already used the new approach to perform more than 175 edits in human cells in laboratory dishes, including fixing genetic mutations that cause sickle cell disease and Tay-Sachs disease.

This Prime Editing is the latest version of "CRISPR - Cas9". Because the procedure can make changes that occur naturally in plants, at least some prime-edited crops should not be regulated as "genetically modified", he added. The research was also led by first author Andrew Anzalone, a Jane Coffin Childs postdoctoral fellow in Liu's lab at the Broad Institute. "The fact that we could directly copy new genetic information into a target site was a revelation".

LIU: Prime editing is really a step, and potentially a significant step, towards this long-term aspiration of the field in which we are trying to be able to make just about any kind of DNA change that one wants at just about any site in the human genome.

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