New molecular tool promises "precise" gene editing

Scientists have invented a “versatile and precise” molecular tool for editing DNA, capable of correcting up to 89 per cent of the errors which cause genetic diseases. The study, published in Nature brings new hope to people with genetic disorders such as sickle cell anaemia and Tay-Sachs disease.
‘Prime editing’ promises greater precision and flexibility over previous technologies, with its ability to accurately insert or delete DNA sections and correct harmful mutations down to a single “letter”. One of the researchers, Dr David Liu, described prime editing as the “word processor” of gene editing, due to its ‘cut and paste’-like properties.
While the traditional method of DNA editing, CRISPR-Cas9, cuts both strands of the DNA like a pair of scissors, the prime editor complex cuts just one of the DNA strands. This is paired with an enzyme (called reverse transcriptase) to generate new DNA from an RNA template.
The prime editor is guided to its target on the DNA by a specifically-engineered “pegRNA” (prime editing guide RNA) molecule. The pegRNA then binds to the flap of cut DNA, preparing it to have new DNA “letters” added. The desired edit is encoded in another region on the pegRNA.
The enzyme paired with the prime editor reads the template RNA, and attaches the right DNA “letters” to the end of the original flap of DNA. Finally, other enzymes in the cell remove the old DNA and seal the new DNA in place. The edited DNA is tidied by the prime editor  and another template RNA, ensuring all the “letters” match on opposite DNA strands.

The process of prime editing. Image: George Tuli

Prime editing results in fewer errors than the CRISPR-Cas9 method, such as unintended or off-target edits. This is because CRISPR-Cas9 only requires one DNA binding point while the new prime editor requires three, so the likelihood of random, incorrect pairings, is greatly reduced using the new editing technique.
While tests in the lab have shown promising results, it is yet to be determined how to deliver the tool effectively and safely to cells in the human body. Using viruses to target the editing complex was considered in the study, as well as non-viral delivery techniques. The researchers plan to do additional studies in animals to work out the best delivery method.

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