The CRISPR gene editing system holds tremendous promise. It has already revolutionized biomedical research by making gene editing a straightforward process. It involves using a guide RNA molecule that has a unique sequence, which matches with a target location in genomic DNA. This guide RNA brings an enzyme called Cas9 to that genetic location, where Cas9 makes a cut in the DNA. Scientists have been modifying and improving on the CRISPR technique since it was created. Many of those improvements are related to the Cas9 enzyme, and ensuring that it makes the proper cut in the correct place.
One type of CRISPR gene editing is known as prime editing. In prime editing, the Cas9 enzyme has been modified so instead of cutting through both strands of the double-stranded DNA molecule, it only cuts one strand. The guide RNA in this case may also carry a novel genetic sequence, which can be inserted where the cut has been made. After this gene editing happens, edited cells divide into new cells, and the new sequence can be incorporated into the daughter cell’s DNA.
Prime editing has the potential to treat Duchenne muscular dystrophy, cystic fibrosis, phenylketonuria, sickle cell disease, beta‐thalassemia, Hunter syndrome, spinal muscular atrophy, and other disorders. Prime editing was recently used to successfully treat a chronic granulomatous disease (CGD) patient, a rare genetic disease affecting white blood cells.
But the process of prime editing is imperfect; it can be very inefficient and may sometimes introduce novel sequences in unintended places, which could lead to major problems.
New research aims to overcome those limitations. Scientists described methods that could be used to significantly reduce the error rate of prime editors, and potentially open up new treatment avenues for a variety of genetic disorders. In this work, which was reported in Nature, the investigators reduced the error rate from about one for every seven edits to an average of one for every 121 edits; depending on the technique used, the researchers reported rates of one error per 101 edits and one per 543 edits.
"Genome editors are used extensively in research labs, so the therapeutic aspect is exciting, but we are really excited to see how people start to integrate our editors into their research workflows,” noted first study author Vikash Chauhan, a research scientist at MIT’s Koch Institute.
“In principle, this technology could eventually be used to address many hundreds of genetic diseases by correcting small mutations directly in cells and tissues. The technologies we have now are really a lot better than earlier gene therapy tools, but there's always a chance for these unintended consequences.”
Sources: Massachusetts Institute of Technology (MIT), Nature