If the “goal is to minimize perturbing the cell or patient beyond making the desired edit,” Liu explains in an email, “creating a mixture of products such as indels is typically undesirable.”ĬRISPR editing to insert a particular genetic sequence, meanwhile, can leave donor DNA floating in the cell. And if too many double-stranded breaks were to be induced at once, they could prove toxic to the cell. Because DNA is processed in sequences of three letters at a time, indels can also offset the genetic code for a particular protein, changing the output of a cell. If you simply snip DNA in the middle of a target gene and let it repair itself, the resulting indels will often deactivate that gene. These insertions and deletions, called “indels,” are a frequent consequence of the classic CRISPR process. However, the repair process might also rope in some stray letters or chop off pre-existing slivers of the genome. The cell detects and swoops in to repair this damage with whatever genetic materials it has available, often a snippet of donor DNA the scientists have inserted into the cell alongside CRISPR. Once the system recognizes the sequence of bases (the “letters” that make up the DNA alphabet) it’s been instructed to look for, it can cleanly cut the two-part DNA strand, creating what’s known as a double-strand break. … If the Model T was prone to overheating, CRISPR Classic is prone to overeating.”ĬRISPR-based editing makes use of a cellular defense mechanism that originated in bacteria to scan for viral DNA and then dice it up. Still, as Megan Molteni wrote for Wired last year, “CRISPR Classic is somewhat clunky, unreliable, and a bit dangerous. Traditional CRISPR is hardly low-tech it’s a Nobel Prize-buzzworthy process so minute that it’s completely invisible without a high-powered microscope. The method is sleeker, less invasive, and offers the potential for precision genetic editing. Where the familiar CRISPR technique fully cleaves a strand of DNA in two, often creating some tiny, inadvertent genetic changes as byproducts, prime editing begins by slicing just one of the two strands of the double helix. If the original CRISPR mechanism is like a pair of miniscule scissors cutting up a sentence of the DNA code, “you can think of prime editors to be like word processors, capable of searching for precise DNA sequences and replacing them,” says David Liu, the chemical biologist at the Broad Institute and Harvard University who led the research. In a paper published in Nature today, researchers added a new technique to the genetic editing toolbox: prime editing. CRISPR revolutionized medical science by introducing an easy-to-use way to modify the genome, but it’s not the only tool at scientists’ disposal. By now, you’ve probably heard of CRISPR technology, the “molecular scissors” that snip DNA at a target sequence and enable genetic editing.
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