Gene Editing At Its Prime. Beginner’s Guide To Prime Editing.
Who knew that we could possibly cure some of the most deadliest diseases, such as cancer, by specifically editing one’s DNA? Well, what if I were to say that we already have sets of technologies in place trying to make an impact when it comes to solving the world’s most chronic diseases. As a matter of fact, companies to this day have made groundbreaking innovations using gene editing with the help of technologies such as CRISPR and Prime Editing. Researchers were able to enhance CRISPR with Prime Editing as it uses the combination of the well-known Cas9 and a reverse transcriptase to create a powerhouse that uses a unique method to precisely alter, insert, and delete specific DNA sequences. To this day, prime editing is becoming much more known to the public. As a result, there are strong anticipations for clinical implementations in the future as its technology seems very prominent and will definitely influence the medical industry 🧬🔬.
In this article, I will discuss:
- What is Prime Editing?
- How Did Scientists Discover Prime Editing?
- How Does It Work?
- Why is Prime Editing Important?
- How is Prime Editing Different From CRISPR?
- What Might the Future Hold for Prime Editing?
So… What is Prime Editing??? 🤔
When trying to understand what exactly Prime Editing is, we first need to familiarize ourselves with Gene editing. Genome editing is exactly what it sounds like. It is a set of technologies that allow scientists to alter an organism’s DNA. These technologies enable the addition, removal, or modification of genetic material at specific sites in the genome. Along with this, there are different types of gene editing. One of the most known and frequently used forms is known as CRISPR. Prime Editing is a much more accurate kind of Gene Editing in comparison to CRISPR.
Several researchers from the Broad Institute of MIT and Harvard have also described Prime Editing as a more versatile, precise, and adaptable piece of genome editing technology when comparing it to CRISPR. Additionally, an article published by nature mentions that Prime Editing even has the potential to fix up to 89 percent of disease-causing genetic abnormalities and illnesses, according to the scientists. Scientists mainly use the technique of Prime Editing to rewrite the genetic code to correct mutations and sequencing mistakes that can cause diseases.
How did Scientists discover Prime Editing?
In order to discover Prime Editing as a whole, scientists had to analyze and clearly understand the fundamentals of the protein CRISPR Cas 9’s roles. After considerable investigation, scientists discovered that CRISPR Cas9’s native purpose is found within the cell’s bacteria 🦠. They also understood that this protein is used extensively in genetic engineering applications and plays a vital role in the immunological defence of some bacteria against DNA viruses and plasmids. Therefore, concluding that its primary purpose is to cut DNA and hence change the genome of a cell.
A paper published by Xtalks mentions that CRISPR allows the bacteria to remember which viruses were infected by it in the past. The bacteria then makes a replica RNA of the viral DNA using these integrated bits, which binds to the protein Cas9. The paper also mentions how Cas9’s primary purpose is to break parts of DNA and then search across all of the bacterium’s DNA for a perfect match using replicated RNA. Therefore, when a match is successfully found, the Cas9 gets straight to work, cutting both strands of DNA that have entered the bacteria, thereby removing the threat. Michael Lim, a visionary in the healthcare field, infers that we should think that the Cas9 complex can be compared to a bodyguard who keeps an eye out 👀 for invaders.
Additionally, Scientists began to employ unmodified and changed forms of Cas9 in combination with a guide RNA. Ultimately a reverse transcriptase, an enzyme used to produce complementary DNA from an RNA template, after discovering the Cas9 protein’s genome editing capacity. Therefore, Prime Editing was developed as a result of the usage of a guide RNA and a reverse transcriptase.
How does it work?
According to the Broad Institute, scientists were able to design a novel gene-editing technology that exclusively generates Single-Stranded DNA cuts using a modified Cas9 enzyme known as Cas9 nickase in order to alter, add, or remove base pairs. Gene editing may be thought of as a pair of molecular scissors that are capable of cutting DNA strands 🧬.
On the other hand, according to David Liu, a Harvard and MIT scientist, Prime Editing is a three-step, sophisticated procedure that is more exact and accurate than other Gene Editing methods. First, The guide RNA must join up with the target DNA. Second, the Primer, a component of the guide RNA, must bind to the target site, and last, the newly inserted DNA must likewise attach to the target site. Along with this, researchers may now alter a broader range of genetic mutations using this technology.
We can envision Prime editing as a genomic editing tool that works similarly to the ‘find and replace’ capability seen in many word processors today. When it comes to Prime editing, it works on a molecular level and is based on a similar notion. It looks for the mutated gene in an organism. It then makes the desired genetic alterations to fix the mutation using targeted insertions, deletions, or even all 12 forms of point mutations.
This video does a great explanation of the process of CRISPR — Cas9.
Below is a Genome-Editing graphic that shows the complete process in further detail.
Why is Prime Editing important?
When a protein that performs a vital role in the body is mutated, it can disrupt normal development and result in a severe medical illness 🤕. Genetic disorders are diseases that are caused by mutations in one or more genes. What’s more frightening is that most genetic abnormalities are inherited, which means that the kids of someone with a genetic defect have a higher risk of acquiring the condition.
Genetic problems impact a substantially more significant proportion of the population than is commonly assumed. To put that in perspective, experts traditionally thought that genetic illnesses affected just roughly 5% of the human population. However, according to research published in the Annals of Internal Medicine in 2017, the percentage of patients with hereditary illnesses is closer to 20%. This indicates that until a remedy for genetic problems is discovered, the percentage of people with a hereditary condition will rapidly increase ⬆️. Finding a treatment will prevent this proportion from rising, as well as enhance the quality of life for countless people!
“She (Tasha’s mother) was scared when I took my first flight. She was scared when I had a headache. She would automatically think I was having a pain crisis.” says Tasha, a 39-year-old registered nurse with Sickle cell disease. (from CDC).
No one deserves to suffer, yet many like Tasha have been deprived of their regular lives and forced to live in chronic agony and sorrow. If these diseases could be treated, individuals like her would be able to live their lives to the utmost, without limitations. Therefore, Prime Editing is critical because it has a strong potential to lessen their suffering 💪.
Reprogramming of the mutated DNA is the only approach to treat most genetic illnesses. In addition, this approach dramatically broadens the scope and capabilities of genome editing, perhaps paving the way for the treatment of hereditary illnesses.
Gene-editing has the potential to treat the majority of genetic illnesses by reprogramming mutated DNA 🧬, but it also has the potential to produce something altogether new and astonishing! This is referred to as “Designer Babies” 👶 by many. As asserted by Oxford Languages, a designer baby is a child whose genetic composition has been chosen or edited to contain a certain gene or to eliminate genes related to illness.
Scientists and researchers believe that it is feasible to create a Designer Baby with no hereditary disorders and a reduced chance of diseases and viruses when using Prime Editing. In addition, it appears that mutating a kid’s DNA in such a way as to give the infant flawless vision, a high IQ 🧠, and even varied athletic abilities is also very much achievable.
Although controversial, Prime Editing even opens the door to designer humans and, in the future, might lead to the application of genome editing in humans for purposes other than treatment, such as augmentation (who knows, you could be the next Spiderman! 🕷)
Not going to lie, I wish I was born a few decades later and could be a Designer Baby myself! 😂
How is Prime Editing different from CRISPR?
Although Prime Editing and CRISPR appear to be identical at first look, they both have their significant distinctions, as seen in the Venn diagram below.
- Prime Editing employs a modified variant of the Cas9 enzyme that is designed to cut just one strand of DNA at a time, as opposed to the unmodified Cas9 used in CRISPR, which breaks both strands of DNA.
- Prime Editing makes use of a customized version of RNA that is much bigger than the usual RNAs used in CRISPR gene editing.
- Furthermore, a reverse transcriptase linked to the Cas9 enzyme is employed to produce complementary DNA from an RNA template during the Prime Editing process.
- Prime editing also has fewer off-target editing effects, as proven by a Broad Institute investigation that examined the precision of each genome editing approach.
- The amount of study that has been done on Prime Editing is one of the most significant disparities between them. CRISPR has been far more heavily researched and has been around for quite some time compared to Prime Editing, which was first released in October 2019.
CRISPR is a more thoroughly tested method 🧪🔬 that uses an unaltered Cas9 without the addition of a reverse transcriptase. As a result, it has greater off-target effects and cuts through both strands of DNA. Prime editing is a newer, more accurate technique for overcoming some of CRISPR’s limitations. It employs a Cas9 variant with a reverse transcriptase attached. It only cuts one strand of DNA at a time, resulting in fewer side effects.
What Might the Future Hold for Prime Editing?
Prime Editing is a novel approach to making modifications to DNA that avoids some of the limitations that the typical CRISPR has. Prime editing has a lot of promise in the future since it is more potent than other genome editing applications. In recent years, prime editing has even been refined for commercial usage on significant crops like rice and wheat.
This displays Prime Editing’s adaptability and potential in a wide range of industries. When it comes to the potential of Prime Editing in genetics, it has the ability to touch the lives of millions of individuals and assist in reducing the effect of hereditary illnesses in our society.
In new, experimental technology, ethics will always play a part. Multiple articles have prefaced that the critical issue is safety 🥽. Researchers and ethicists who have published and talked about genome editing essentially believe that it should not be used for clinical reasons until it has been shown safe via substantial research. This is due to off-target genomic modifications, and the inability to predict the long-term repercussions of using this technology instills a great deal of anxiety and skepticism.
Lastly, while considering the future of designer humans, is it permissible to change an embryo? The alterations would have long-term consequences for the embryo and future generations, so where does permission come into play? Along with this, researchers and biophysicists are also concerned about acquiring properly informed authorization from prospective parents while the hazards of germline treatment are uncertain. Furthermore, employing this technology would come at a cost, most likely a high one. Finally, how will disadvantaged families in need of the same therapy be able to have their genes modified? These are only a few of the potential issues that could face prime editing in the future 🤔.
Who would have believed that we could possibly take a bacterium’s viral defensive mechanism and turn it into a game-changing gene-editing tool? As a result, we can do everything connected to genetics with this technology and practically rewrite our future 🚀.
Key Takeaways:
- Prime Editing is a technique that scientists employ to rewrite the genetic code in order to correct mutations and eradicate sequence faults that cause illnesses.
- We can considerably improve the possibilities of genome editing and help reduce ⬇️ the effect of hereditary illnesses in our society by using Prime Editing technology.
- Although they appear to be the same at first look, CRISPR and Prime Editing have significant distinctions, with Prime Editing providing more chances and being more comprehensive and accurate.
- The future of Prime Editing looks positive, but more testing and analysis is needed before this technology can be released and have an influence on our society.
Hopefully, I’ve enlightened you about Prime Editing and its future. Furthermore, I hope you discovered something new and developed a better knowledge of Prime Editing as a whole! 🙃
