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 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?
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.
Once these four bases are rearranged in various sequences, it provides us with this 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 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 more efficient?
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 at once, 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 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.
Environmental, Ethical and Health Impacts of Prime Editing
How Prime Editing Impacts the Environment:
Medicine and healthcare aren’t the only two fields where Prime Editing is opening doors. It also has the potential to make a major breakthrough in environmental science, one of the ways being through limiting the impact of fossil fuels and Greenhouse Gases.
· Prime Editing can play a major role in decreasing our dependence on fossil fuels, resulting in fewer GHG emissions.
· A few of the biological sources and contributors to fossil fuels are cows, flooded rice fields and wetlands.
· Prime Editing can be used to tweak the genetics of cows, or the grass that they consume, in turn reducing the number of belches that they produce, per meal.
(This is an awesome article explaining how genome editing is tweaking cows to reduce heat stress, as a result of climate change!)
· An unintended error in engineering the genetics of a virus or bacteria can lead to fatal consequences, as it can cause a serious epidemic when released. (Can result in a stronger type of virus or bacteria)
· Also, one cannot predict the changes that a new genetically modified species will have on its surrounding environment.
· New genetically engineered species can pose a threat in the ecology of a region, as there’s a possibility of causing an imbalance.
Ethical Implications of Prime Editing
It’s crucial to understand the risks that come along with this cutting edge technology as well.
· This idea of “playing God” has posed a major ethical concern concerning Prime editing and genome editing in general. (Genome editing is the manipulation of life, and this technology is giving rise to “designer babies” who are healthier and cleverer.
· One of the main ethical considerations to keep in mind are that genetic changes made in the germline would pass onto future generations. (Genetic changes are permanent, which might cause unintended consequences for future descendants).
· Prime Editing allows scientists to rewrite the gene pool of future generations
· Many people have moral or religious objections to using human embryos for research
How Prime Editing Impacts Human Health:
· The genome editing does not only impact the embryo but also impacts future generations, reminding researchers of the risk that comes with this technology as well.
· Germline human genome editing alters the genome of a human embryo at its earliest stages thus the effect will be present in every cell, impacting future descendants.
· Also, an unintended deletion or insertion of genes can negatively impact the embryo, causing other genetic diseases that were not originally present.
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. (By removing the four extra chromosomes causing Tay-Sachs)
It can also be used to eliminate an extra chromosome, which results in Klinefelter Syndrome, XXY. (We looked at this in class — Meiowsis Gizmo)
Once prime editing has undergone many trials and research, there’s the potential to cure many medical conditions with it as well. Who knows…
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 only limited to humans but can also be used in agriculture, and environmental science to limit the impacts of fossil fuels, and greenhouse gas emissions!
Well, I guess we’ll have to wait and see what the future holds for Prime Editing!
Originally published on December 15, 2020.
Works Cited
Bergman, M. T. (2019, October 28). Harvard researchers share views on future, ethics of gene editing. Retrieved from https://news.harvard.edu/gazette/story/2019/01/perspectives-on-gene-editing/
Ledford, H. (2019, October 21). Super-precise new CRISPR Tool Could Tackle a Plethora of Genetic Diseases. Retrieved from https://www.nature.com/articles/d41586-019-03164-5#:~:text=CRISPR-Cas9 and prime editing, damage and make the edits.&text=Prime editing bypasses these problems (see ‘Precision editor’).
Mulvihill, J. J., Capps, B., Joly, Y., Lysaght, T., Zwart, H. A., & Chadwick, R. (2017, February 23). Ethical issues of CRISPR technology and gene editing through the lens of solidarity. Retrieved from https://academic.oup.com/bmb/article/122/1/17/3045812
Page, M. L. (2020, October 05). Cattle are being gene edited to help them survive climate change. Retrieved from https://www.newscientist.com/article/2256097-cattle-are-being-gene-edited-to-help-them-survive-climate-change/
Sample, I. (2019, October 21). New Gene Editing Tool Could Fix Most Harmful DNA Mutations. Retrieved from https://www.theguardian.com/science/2019/oct/21/new-gene-editing-tool-could-fix-most-harmful-dna-mutations
Soloviy, V., Cross, D. T., & Partanen, R. (2019, April 10). Gene Editing has Serious Ethical and Environmental Implications. Retrieved from https://www.sustainability-times.com/environmental-protection/gene-editing-has-serious-ethical-and-environmental-implications/
Yasinski, E. (n.d.). New “Prime Editing” Method Makes Only Single-Stranded DNA Cuts. Retrieved from https://www.the-scientist.com/news-opinion/new-prime-editing-method-makes-only-single-stranded-dna-cuts-66608
Originally published at https://824184.medium.com on December 16, 2020.
