Correcting 89% of the 75,000 mutations associated with congenital diseases suddenly seems possible: this is 'prime editing'
In 2016 David Liu revolutionized the CRISPR world with "base editors". The editors of bases usually receive the nickname of "molecular typex" because they are synthetic proteins capable of converting some nitrogenous bases into others. Those bases are, in a quite literal sense, the letters with which DNA is written.
That was a bombshell. However, despite Liu's attempts to improve the technique, the base editors were found to produce unwanted DNA mutations. They produced them, in fact, at a very high level. This, as you can imagine, was a very serious difficulty for publishers who began to stop using it.
But Liu is an insistent guy.
What is Prime editing and why are the experts so excited
Now the magazine Nature publishes a work by his team that collects results from 175 experiments with human cells in the laboratory. Thanks to 'Prime editing', which they have named the technique, they have been able to correct the genetic mutations that are behind diseases such as Tay-Sachs or sickle cell anemia.
However, this goes much further. The idea behind 'Prime editing' is simply a genius. Liu's team has used a variant weird of the Cas9 protein with a reverse transcriptase. Unlike the Cas9 we usually use, the variant that Liu uses to position and cut DNA only segments one of the DNA strands (so it does not activate the nuclear repair mechanisms that generate unwanted mutations).
And then reverse transcriptase comes into action, that is, the synthesis of DNA from RNA. This is a very rare thing: as we all know, it is DNA that "produces" RNA, but some microorganisms such as RNA viruses have the ability to do the reverse maneuver to 'infiltrate' the genome of the cells they attack.
In this way, the 'prime editing' is capable of introducing completely new genetic information into the genome, without unwanted mutations and with a technology that has lifted the entire audience of molecular biologists on the planet and has applauded them. Of course, with the memory of the base editors still fresh in memory, we have to be careful.
Liu and his team claim that this technique could address 89% of the more than 75,000 known mutations associated with congenital diseases. However, it is worth remembering that much remains to be investigated, the work has only been done on cells in the laboratory and now there is a long process to go until the first tests with humans. A process that can derail at any time. Still and with everything, today is a good day.
Image | Broad Institute