Prime Editing: Changing the World One Strand at a Time

Prime Editing: Taking Gene Editing up a Notch (Image from Citi.io)

In 2015, Amalya passed away after living for only an hour and twenty minutes. He was born with a disease called anencephaly, a genetic disorder that 1 in 5000 Americans face. What if there was something to save Amalya and many other babies with these conditions, striving to have them live longer, healthier lives and saving parents from the grief of losing a new born? What if this and other fascinating prospects be possible, such as editing genes to change physical appearance, increase IQ and cure a disease someone could have, before they were born? Could this be a realistic part of our future? If yes, then how?

Introduction

Creative and ambitious innovators and scientists continue to develop machines and new technologies that are assisting humanity in solving some of the world’s biggest problems along with changing how we live for the better. Some of these technologies are creating a future we could have never imagined.

Technologies Changing the World (Image from PropertyCasualty360.com)

Although, we are using the aid of technologies to solve major world issues, many health-related problems still persist. Cancers and genetic diseases cause tremendous problems and enormously contribute to health care costs globally. Despite advancement in technology, many healthcare related problems remain unsolved. Is there not a technology that can change this? Well, there is a potential technology that can lead us to the path of a cure. This technology is not only a major step forward in finding the cure for cancers but can also be the cure for various genetic diseases that millions face today. It has the potential to save lives all across the globe and prevent millions of parents from mourning the deaths of young kids. Along with solving some of these issues, it also has the potential to enhance physical appearances and increase IQ in a person before their birth. As you can tell, this technology is quite the game changer. So without further ado, I present to you Prime Editing!

This article aims to inform you about the following

What is Prime Editing and How Does it Work?

In order to better understand what Prime Editing is, we need to familiarize ourselves with Gene Editing. Gene Editing or Genome Editing is a technology that enables scientists to add, remove, and alter the DNA for any living organism. A great way to comprehend the notion of Gene Editing is that it is like a pair of molecular scissors capable of cutting DNA strands. There are different forms of Gene Editing and one of the most well-known and frequently used forms is the CRISPR technology. Prime Editing is a more precise form of Gene Editing compared to CRISPR. Prime Editing can be defined as a “Search and Replace” form of Gene Editing technology that can directly write new genetic information in any directed DNA site.

Figure 1: Three step process of Prime Editing (Image from Health Care in Europe.com)

In her article for TheScientist, Emma Yasinski mentions that Prime Editing rewrites DNA by cutting only a single strand of DNA in order to add, remove, or replace base pairs. David Liu, a biologist at Harvard and MIT and an influential figure in the advancement of Gene Editing, mentions that Prime Editing is a three-step, complex process making it more precise and accurate compared to other Gene Editing technologies. Firstly, the guide RNA must pair with the target DNA. Secondly, a part of the guide RNA, known as the Primer has to attach to the target site, and lastly the newly introduced DNA has to also attach with the target site. All three of these steps need to be executed in order for the Prime Editing to work. (Figure 1)

How is Prime Editing Different from CRISPR? Is it Better or Worse?

The CRISPR Cas9 technology was created many years ago. Prime Editing is a new genome editing technology created in 2019.

Both Prime Editing method and CRISPR use the Cas9 protein to cut the DNA at a specific point in the entire genome, but Prime Editing alters the Cas9 to only cut one strand of the DNA whereas CRISPR cuts both strands. Prime Editing also consists of two major additional components including a Prime Editing Guide RNA also known as the pegRNA and another enzyme called Reverse Transcriptase. Along with this difference, Prime Editing requires three steps whereas the CRISPR technology only uses the first step. Unlike Prime Editing, CRISPR cuts both strands of DNA which leaves the cell to repair itself often causing unwanted and dangerous mutations in the cell. According to Dr. Liu, Prime Editing is a much more complex form of gene but far more accurate.

He explicates the difference between CRISPR and Prime Editing through a great analogy. He explains that CRISPR acts like a pair of scissors cutting up a sentence of the DNA whereas “you can think of prime editors to be like word processors, capable of searching for precise DNA sequences and replacing them,”. Since I love playing and watching basketball, I came up with an analogy for myself. In a basketball roster, there are usually three lineups, the starting line up, bench, and third lineup. CRISPR would be able to mix and match different line ups to create a team, whereas Prime Editing would be able to mix and match each player to create a team.

The CRISPR technology was a huge advancement in Gene Editing. There was much excitement when it was first discovered, but there were frequent errors in the process. Then there was base editing which was thought to reduce inaccuracy. However after more recent work, scientists have learned through experiments that it is not as accurate and precise as it had been conceived. The scientists combined what they had learned from these two technologies and created a new technology called Prime Editing.

Figure 2: Differences between CRISPR, BASE, and PRIME Editing (Image From Genoway.com)

In order to really see how much more accurate Prime Editing is compared to CRISPR, Dr. Liu and his team executed a test where CRISPR and Prime Editing would edit four genetic mutations of a human cell. CRISPR caused 16 off-target DNA changes whereas Prime Editing only caused 4, demonstrating its accuracy and precision. Due to its accuracy and precision, Prime Editing is considered safer. (Figure 2)

This video will help in better grasping the concept of the CRISPR technology.

Why is it Important and Why Should I Care?

Remember Amalya, the baby boy who unfortunately passed away within 2 hours of birth due to a genetic disease called anencephaly. In the same Business Insider article where I discovered the story of Amalya, there was also a mention of another young boy, son of Sarah Gray who died after living for only 6 days because of the same disease, Anencephaly. The infant suffered constant seizures for 6 days before he passed away. His mom spoke up about Gene Editing. She said that if there is a way to save these kids and their parents from the anguish, then something should be done. Anencephaly is only one of numerous genetic disorders that millions of kids suffer. Below is a link of Sarah Gray making a passionate plea to advance Gene and Prime Editing.

Other hereditary diseases such as cancer, diabetes, cystic fibrosis, heart disease, and Alzheimers affect millions and often cause death. This is where Gene and Prime Editing can come into play.

Gene Editing has the potential to edit these genes so that these genetic and hereditary diseases can be avoided. The CRISPR technology provided hope that there may be a way to edit genes so that people can avoid contracting genetic disorders but it was still unsafe and had many side effects that could be fatal. Recently, Prime Editing has become a safer Gene Editing technology. In order to understand the importance and potential of Prime Editing, this chart and the following explanation portray what Prime Editing can accomplish.

Different Pathogenic Genetic Variants (Screenshot from Nature.com)

The chart above demonstrates the 75,122 different pathogenic genetic variants that humans can face. These are 75,122 genetic diseases or disorders that can be passed on from one generation to another. According to Dr. Liu, Prime Editing can solve 89 percent of these diseases and disorders. Therefore, Prime Editing has the potential to greatly impact and save the lives of so many by providing a safe and healthy cure.

Prime Editing on Crops (Image From PioneeringMinds.com)

Not only does Prime Editing have potential to save millions from genetic diseases and health issues, it also has potential in addressing other challenging and pressing issues.

Prime Editing can be applied to all organisms and not just humans. Since the human population is growing and is expected to reach 9 billion by the year 2050, there will be a greater need to make resources available. Prime Editing will play a pivotal role in creating more efficient and fruitful crops so that the needs of the growing population can be met.

What Might the Future Hold for Prime Editing? Is it Realistic and Feasible? How Will it Affect Humanity?

If proven safe and successful, Prime Editing will likely be a huge part of our future. Diseases like cancer and diabetes still take the lives of millions all around the world. In the future, if Prime Editing was to be legalized, it has the potential to cure people of these diseases and will therefore have a major impact on humanity. 1 in every 11 adults suffers from diabetes. This is about 415 million adults all around the world. With the growing population, there will likely be more people who will suffer from cancer, diabetes or other genetic disorders. If Prime Editing can be proven safe and usable, it will surely save and change the lives of billions of people all over the globe.

Prime Editing can tremendously affect humanity. However it is still far from being completely safe for human trials. Scientists continue to work on experimenting the technology in order to ensure that it is ready for testing on humans, but this fascinating new technology is not limited to curing genetic diseases alone.

In the future, it may be able to change physical appearance in a person! For example, scientists may be able to edit genes in an unborn baby to make them grow taller and have more IQ. That’s pretty cool! Many refer to these additions to the fetus as being “Designer Babies”. I can already see myself wanting to have used this because I love playing basketball and thus have worked hard and become very good at the sport. Though I am very skilled, my parents are not very tall, and as a result, most of my peers and opponents are taller and more athletic than myself. This really limits my potential and I often wish I was taller because I could have fully utilized my potential.

Designing kids in the Future (Image from Quora.com)

Though all this seems incredibly captivating, many raise a finger at Gene Editing as a whole.

Firstly, Gene Editing is still not safe and side effects of Gene Editing are not fully recognized. Even the slightest of mistakes can potentially create problems for an entire lineage of a person.

Secondly, many people believe that the use of Gene Editing will reduce diversity in humans, as people will become capable of artificially choosing desired traits and outcomes. It will no longer keep us unique and will be going against nature.

Thirdly, many people argue that Gene Editing will be used for something like “Designer Babies” and will be used for other unethical reasons which are not directly saving lives. If everyone is created with high IQ, people will not need to work as hard as they are naturally born smarter than everyone else. Designer Babies may cause unfair advantages for the wealthier class. Therefore, many people believe that Gene Editing can be used unethically.

So Prime Editing is without a doubt super cool, but understandably so, many concerns remain about it being used on humans.

Conclusion

Here is a quick recap of everything we learned. Prime Editing is a more precise and flexible genome editing technology than the very famous CRISPR Gene Editor. Instead of cutting both DNA strands like CRISPR, it only nicks one and increases the accuracy. It makes less unwanted cuts and minimizes errors. Prime Editing is very important because it could potentially be the cure to many genetic/hereditary diseases and disorders that millions face today. It has the potential to create enhanced humans but at the same time can be used for multiple unethical reasons. Overall, I believe that Prime Editing indeed has the potential to save lives all around the world. It still needs to be further explored and experimented in order to ensure its safety, but if proven safe and successful, it should be used to cure diseases and not to create unfair advantages in humans.

I hope to have informed you about Prime Editing and keep a look out, for we may see a new world, changed one strand at a time.

Citations

(1) Lewis, T. (2015, December 08). A parent whose child died tragically says a controversial technique could ‘save a lot of heartbreak’. Retrieved from https://www.businessinsider.com/parent-who-lost-a-child-says-gene-editing-is-important-2015-12

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

Thulin, L. (2019, October 21). A New Gene Editing Tool Could Make CRISPR More Precise. Retrieved from https://www.smithsonianmag.com/science-nature/prime-editing-new-form-crispr-technology-make-gene-editing-more-precisie-180973381

Gallagher, J. (2019, October 21). Prime editing: DNA tool could correct 89% of genetic defects. Retrieved from https://www.bbc.com/news/health-50125843

Potenza, A. (2017, August 03). Editing human embryos is okay — but don’t turn them into people yet, geneticists say. Retrieved from https://www.theverge.com/2017/8/3/16071810/gene-editing-embryos-crispr-research-ethics

Niiler, E. (2018, August 29). Why Gene Editing Is the Next Food Revolution. Retrieved from https://www.nationalgeographic.com/environment/future-of-food/food-technology-gene-editing/

Niglia, S. (2020, January 18). Gene Editing Pros and Cons — Advantages and Disadvantages. Retrieved from https://explorebiotech.com/gene-editing-pros-and-cons/

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Aahil Noorali

Aahil Noorali

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