Prime Editing — Rewriting the Future of Genome Editing
A revolutionizing discovery in medicine.
Every year, nearly 7.3 million infants worldwide are born with some sort of genetic disease. An estimated 3.3 million of these infants would then die by the age of 5.
And the reason for these genetic diseases in the first place, is an error (mutation) in the DNA sequence.
Think of DNA as an instruction manual in which our genes are written. Even a single error in our genes can lead to fatal consequences.
But what if there was a way to (literally) edit genomes to prevent these genetic diseases in the first place?
Well…There is. It’s Prime Editing!
Prime Editing is a genome editing technique that allows scientists and researchers to edit and replace specific parts of the DNA. It’s easier to think of it as the “search and replace” function in a word processing software. Its job is to essentially find any disease-causing mutation (target DNA) in DNA sequences and replace them with an edited one to correct the genome.
After the prime editing system finds a target site in the DNA, it rewrites the sequence of genetic information to directly replace that original DNA sequence with an edited sequence.
“Prime Editing can correct nearly 89% of disease-causing variations in DNA.” — David Lui (Co-founder of prime editing)
Breaking down Prime Editing:
Prime Editing consists of three main components:
pegRNA (Prime Editing guide)
The main function of the pegRNA is to specify where the target site is, or where the DNA needs to be cut. It also encodes new genetic information which later replaces the original DNA sequence.
→ What’s so interesting about the pegRNA, is that it’s programmed beforehand by scientists to locate ANY part of the DNA. (It can only be programmed if scientists already know the sequence of the targeted DNA site).
After it’s programmed, the pegRNA is inserted into the Cas9 enzyme, directing it to the targeted DNA sequence. The pegRNA later binds to the nicked part of the DNA.
The pegRNA also includes an RNA blueprint for the new DNA sequence, that is to be added into the nicked spot in the genome.
Cas9 Protein
The main function of the Cas9 enzyme is to cut the targeted section of the DNA. (Only nicks one DNA strand) But what happens after the Cas9 enzyme nicks a part of the DNA strand?
Reverse Transcriptase
The Reverse Transcriptase is another enzyme that is attached to the pegRNA. The RT’s role is to encode the genetic information located in the pegRNA, which is then inserted into the targeted site in the DNA.
I’ll explain what I mean by “genetic information.”
Our DNA is made up of these DNA molecules in which our genetic information is stored. The DNA molecules in the human body are made up of four nitrogen bases.
Adenine (A), thymine (T), cytosine (C), and guanine (G).
Once these four bases are rearranged in various sequences, it provides us with these set of instructions, which is what makes up our genetic information.
After one of the DNA strands has been successfully edited, there is now a mismatch, since the cell hasn’t bonded the base pairs (A and T bond, C and G bond) to the edited DNA strand. So now, the cell uses the edited DNA sequence as a blueprint in order to edit the second strand, thus giving us a fully edited DNA sequence.
Prime Editing VS. CRISPR:
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a genome-editing technique similar to that of Prime Editing. Now both of these gene-editing methods work, but which one’s the better one?
CRISPR and Prime Editing are really similar, as they both cut DNA in a specific part of the genome. Although, one of the major differences between the two, is that CRISPR nicks both DNA strands, whereas Prime Editing only one.
This gives Prime Editing a huge advantage, as this minimizes the chances of any errors in the DNA or any unwanted genome edits.
One downside to the CRISPR-Cas9 system is that it has to rely on the cell’s own repair mechanism to make changes in the DNA. This can lead to unwanted mutations within the DNA strand, which are also irreversible.
CRISPR can also produce off-target mutations leading to fatal consequences, one of them being cancer. Many studies using CRISPR-Cas9, found that nearly 50% of DNA mutations were occurring off-target.
Since CRISPR is more prone to errors, Prime Editing would be the better option, as it provides scientists with much more control and precision over DNA mutations.
What’s Next for Prime Editing?
Prime Editing is a HUGE technological advancement in the field of genomics, allowing us to edit ANY genetic mutation in DNA, curing various human genetic diseases, such as Sickle Cell Anemia and Tay-Sachs Disease. (Like how cool is that!)
Once prime editing has undergone many trials and research, there’s the potential to cure many medical conditions with it as well. Who knows…
—> Ethical Concerns Regarding Gene Editing
It’s crucial to understand the risks that come along with this cutting edge technology as well.
One of the major ethical consequences of genome editing is that it not only affects the individual but the mutations can also be inherited by future generations.
Genome editing raises many questions among people regarding ethics, as many people have moral or religious objections to using human embryos for research.
Also, with gene editing, you would have this culture of people just obsessed with being enhanced, reminding scientists of the ethical responsibility that comes along with this advanced technology.
Prime Editing has the potential to cure diseases such as Alzheimer's and Parkinson's, which is just mind-blowing!
What’s far more interesting is that it’s not limited to only humans, but can also be used in agriculture to further improve crops.
Well, I guess we’ll have to wait and see what the future holds for Prime Editing!
Works Cited
Shelly Fan, et al. “Everything You Need to Know About Superstar CRISPR Prime Editing.” Singularity Hub, 4 Nov. 2019, singularityhub.com/2019/11/05/everything-you-need-to-know-about-superstar-crispr-prime-editing/.
Begley, Sharon. “Scientist David Liu Takes Your Questions on CRISPR and Prime Editing.” STAT, 6 Nov. 2019, www.statnews.com/2019/11/06/questions-david-liu-crispr-prime-editing-answers/.
Cohen, Jon. “Prime Editing Promises to Be a Cut above CRISPR.” Science, American Association for the Advancement of Science, 25 Oct. 2019, science.sciencemag.org/content/366/6464/406.
Ledford, Heidi. “Super-Precise New CRISPR Tool Could Tackle a Plethora of Genetic Diseases.” Nature News, Nature Publishing Group, 21 Oct. 2019, www.nature.com/articles/d41586-019-03164-5.
Lewis, Tanya. “New Gene-Editing Tool Could Fix Genetic Defects-with Fewer Unwanted Effects.” Scientific American, Scientific American, 21 Oct. 2019, www.scientificamerican.com/article/new-gene-editing-tool-could-fix-genetic-defects-with-fewer-unwanted-effects1/.
Masci, David. “Human Enhancement: Scientific and Ethical Dimensions of Genetic Engineering, Brain Chips and Synthetic Blood.” Pew Research Center Science & Society, Pew Research Center, 30 May 2020, www.pewresearch.org/science/2016/07/26/human-enhancement-the-scientific-and-ethical-dimensions-of-striving-for-perfection/.
Orlando, Alex. “Will Prime Editors Be the New CRISPR?” Discover Magazine, Discover Magazine, 30 Dec. 2019, www.discovermagazine.com/health/will-prime-editors-be-the-new-crispr.
