Medical research in the contemporary era has made its shift from drug discovery towards more advanced methods of preventing and treating various conditions by directly altering living organisms' genetic code. One prominent method for "genome editing" is the use of CRISPR, a technology first discovered by Francisco Mojica from the University of Alicante in 1993. Since then, CRISPR has been used to edit genomes by cutting up DNA at a specified location and having the body's natural repair mechanism to add, remove, or replace segments of genetic material into DNA. While the technology may seem simple enough, there still remain difficulties in executing the technique. CRISPR tends to cut up the DNA in locations where it should not, and the cell's repair work is often unreliable. A novel technique has been discovered by researchers from the Broad Institute in Cambridge, Massachusetts, which they coined as "prime editing" in their official publication in Nature.
Prime editing: cutting and editing into one swift action
Prime editing circumvents the tendency for collateral damage and unwanted mutations seen in current CRISPR technology by simply "nicking" the DNA at one strand and editing the targeted DNA location directly after. The technique is made possible by using a modified Cas9, the enzyme responsible for cutting the DNA at both strands. The Cas9 enzyme fused with a reverse transcriptase provides both cutting and editing abilities into one handy "tool," which makes prime editing a very efficient method for genome editing compared to previous techniques.
Laboratory head David Liu from the Broad Institute alongside his postdoc Andrew Anzalone and other colleagues have tested their newly discovered prime editors on different human and mouse cells to serve as a proof of concept. They have done more than 175 edits, including the correction of mutations causing sickle-cell anemia and Tay–Sachs disease. Other conditions previously treated unsuccessfully by other genome editing techniques were also tested by the team with the newly discovered prime editors.
Lab results reveal high potential for prime editing techniques
The research reveals that prime editing provides better efficiencies, less off-target cutting, and fewer byproducts compared to previous CRISPR techniques. They estimate that around 89% of genetic mutations that can cause human disease can be corrected with the use of the new technology. This discovery has very big implications for medical treatments in the future. Despite these developments, the prime editors' trade-off from older enzymes is its larger size. Delivery of these molecules into cells could prove difficult since the viruses normally used by scientists is too small for prime editors to fit. Needles that can inject into embryos have very narrow passageways, which can be clogged if prime editors were to be dispensed. Gaetan Burgio, a geneticist from the Australian National University, cites those examples as potential drawbacks for commercial use of the technique in an interview with Wired.
In spite of these drawbacks, Liu co-founded a company in September called Prime Medicine revolving around the technology that his team developed at the Broad Institute. The company shall focus on developing technology with better reliability. However, it may take years before human trials could begin.
