Curing Sickle Cell Disease and So Much More With Prime Editing
Prime Editing
When you hear “gene editing,” the first thing that you likely think of is science fiction, mutant chimeras your parents used to tell you about to get you to behave or ginormous parks filled with prehistoric dinosaurs, but, gene editing is not a work of fiction at all, and can actually cure many diseases that we had no hope of curing in the past.
This brings us into Prime Editing. Prime editing is a gene-editing technology that finds specific genome base pairs within your DNA and switches them out to more desirable ones, think switching out a faulty gear. But how? You might be thinking and to answer that question we will have a look into what exactly makes up our DNA.
This is a visual representation of the double helix that is our DNA, you might remember it from biology. Now pay attention to the different shapes and colors that connect the two sides, these are known as the nucleotide base pairs and function as the instructions of our DNA. Each shape you see represents one of 4 types of these nucleobases, either Thymine, Adenine, Guanine, or Cytosine. For purposes of convenience, we’ll refer to these nucleobase types by the first letters of their names, T, A, G and C respectively.
A keen eye might also have noticed that there are no C-T or G-A pairs, that is because C can only pair with G, A can only pair with T and vice versa. Remember this, it will come to play in a little bit. These pairs, and the order and position they are in, make up the instructions of our DNA.
Everyday, our cells ‘copy and paste’ our DNA in order to duplicate in a process called mitosis. Sometimes though, our cells don’t replicate our DNA perfectly, resulting in mutations, the most common of which are Point Mutations. Point mutations are where a single nucleotide base pair (remember these?) is changes from either a T-A to a C-G or the other way around. This is the origin of evolution and is also the reason for many genetic disorders such as Sickle Cell disease and Progeria, a disease that makes children age rapidly and kills most before the age of 13.
Prime editing brings the promise of curing these diseases by changing the specific nucleotide base pairs that cause these diseases into pairs that don’t. Harvard Chemical Biologist, David R. Liu, explains exactly how his team came to develop prime editing in his Ted Talk. Here’s the link: https://www.youtube.com/watch?v=ONs9FCY74p0
What Liu says is that the team took CRISPR, which is a revolutionary gene editing protein in its own right (we’ll talk more about the differences in a second), and disabled the enzyme that cuts out specific DNA sequences. The team then added another enzyme which, instead of cutting DNA out, chemically reacted with the C base type turning it into a T base type. Crazy stuff right?
But if you remember from earlier, C can only pair with G and T can only pair with A (good thing you remembered it from earlier) so changing the C in a C-G pair to a T still doesn’t work. T-G pairs are unstable. To remedy this, the team engineered the same enzyme that turned the C into a T to be able to also nick the G in that same pair. The body then sees a damaged nucleotide base, and replaces it, switching it out for an A pair to match the T. The same can be done the other way around.
Why is this a breakthrough? Couldn’t CRISPR already edit genes?
While CRISPR could edit genes as well, there are two fundamental differences between the two. First, CRISPR targets DNA sequences while Prime Editing targets specific base pairs, and second, CRISPR just cuts out DNA while Prime Editing actually changes it on a molecular level.
The same tracking protein was used between the two of them, CRISPR’s Cas-9, but Prime editors have an enzyme that converts certain nucleotide bases into other bases while CRISPR can only cut DNA sequences, making the DNA unstable and deactivating it.
This is incredibly important as, with CRISPR, we weren’t able to cure genetic diseases because CRISPR only cuts out parts of the genome. If you’re still thinking in terms of gears from earlier, think of taking out the faulty gear entirely. If you still had the faulty gear, the machine would work improperly but, if you take the faulty gear out, the machine doesn’t work at all. This is essentially what CRISPR does. With prime editing though, we just change the base pairs, returning the genome to proper function. Think swapping the faulty gear for a new one.
This is exactly what we need to cure many genetic diseases, many of which we are absolutely powerless to stop otherwise, even though we know exactly which point mutation is causing it.
What this means for the future
Prime editing has incredible implications on the future of gene editing. A countless number of genetic diseases could be cured, saving countless lives, we might even have designer babies. Athletes could literally change their DNA instead of taking steroids. Family disease history could no longer be of any worry as we could erase all genetic predispositions to diseases. It’s both terrifying and intriguing to think of all we could do with this.