The future of gene editing —
So, let’s say you’re trying to solve a complex math problem. After you reach the end of 5 pages of calculations, you realize that you misread the question. You wrote a digit of an important parameter, which was used for all of your calculations, incorrectly!
What are you going to do?
Well, you would have to erase each instant you used that number, rewrite, and recalculate everything again. THIS WOULD BE VERY FRUSTRATING, RIGHT?
What if we could instantly search and detect the incorrect digits, replace them with the correct ones and simultaneously do an automatic recalculation?
Well, that would be amazing wouldn’t it?
Welcome to the world of gene editing.
Instead of correcting digits from variables in a math problem, genetic engineers manipulate nucleotides in human DNA to solve problems relating to disease and human evolution!
There are 4 basic nucleotides that they can work with.
Thymine(T), Cytosine(C), Adenine(A), and Guanine(G).
A only bonds with T, C only bonds with G.
By editing human DNA, we may be able to cure diseases without surgery and expand our medical capabilities with technology. DNA editing could fix harmful genetic mutations and save millions of lives.
I’m so excited to share what I’ve learned about the latest gene editing tool — Prime Editing.
Here we go…
Over the years, genetic engineers have only used something called CRISPR to edit genomes by cutting and pasting DNA sequences. CRISPR is an older version of gene editing. If Prime Editing is like the current EXCEL, CRISPR would be an app called, “VisiCalc,” which is like the grandfather of EXCEL.
Although this was revolutionary in the history of molecular biology in 2012, it had some downsides, which we will go in detail later. Dr. David Liu from the Broad Institute of MIT and Harvard invented “Prime Editing” in November 2019 to overcome these challenges, which was essentially a super upgraded version of CRISPR.
Let’s start from understanding what gene editing (CRISPR) is.
I explained earlier that CRISPR is a cut and paste DNA editor, but what does that really mean?
Using the example of having an incorrect digit in your math calculations again, here’s how you would proceed in that situation.
- Firstly, you would look for the wrong digit in the number.
- Secondly, you would use an eraser to remove the incorrect digits.
- Finally, you would use a pencil to rewrite the correct digits.
CRISPR is just like that.
Simple. Yet, powerful like how human functions.
Let’s compare how CRISPR works in three steps.
Step 1: FIND
A type of nucleic acid called gRNA (G stands for Guide) is like our eyes which is programmed by scientists so that it would look for the targeted segment of DNA that we want to edit.
Step2: CUT
Cas-9 protein is like an eraser that is used to cut sections called PAM at the targeted DNA. What is Cas-9? It is an Endonucleases and is guided by gRNA (our eyes).
Step3: EDIT
At this stage, DNA recognizes its damage and tries to repair itself. Scientists use the DNA repair machinery to make changes in the genomes. DNA repair machinery is like a pencil. Then, the DNA primers (short strands of RNA) tell the DNA which base-pairs to bond so that it can repair by itself.
So after this step, the DNA gets edited and your disease would be cured!
If you’re still a bit confused. Don’t worry. To summarize…
First, rGNA (a nucleic acid) guides Cas-9 (a protein) to the targeted DNA. Then, Cas-9 cuts the DNA. Finally, the DNA repair machinery edits the DNA. Now, you’re fixed!
CRISPR sounds awesome, right?
Then why did Dr. Liu have to create an upgraded version of it?
In CRISPR, Cas-9 cuts the targeted DNA, more specifically the PAM (protospacer adjacent motif). When this occurs, it cuts the double strands of a double helix and there’s a possibility of unintentionally damaging the normal segments of the DNA. So in the situation that we used earlier, it’s like accidentally erasing a digit of a number when solving a math problem. When operating CRISPR, it has a risk of having unwanted changes, which can cause a mutation. This is dangerous! It’s like doctors giving you another disease instead of curing the one you already had. Gene editing should not make any mistakes, the consequences are huge. To overcome this challenge, Dr. Liu and his team invented, “Prime Editing,” based on the CRISPR technology.
So what’s the upgraded version of CRISPR?
“Prime editors offer more targeting flexibility and greater editing precision,” says David Liu.
While CRISPR is a cut and paste gene editing tool, Prime Editing is like a search and replace editing tool. This is like finding the key word on a word document by clicking Command + F and replacing the words with what you want. Instead of cutting double strands of DNA, Prime Editing only cuts one and uses a new enzyme to convert a single DNA letter (nucleotide) into any other. This idea came from Dr. Liu’s earlier project called, “base editing.” Since, many mutations were caused by having a single incorrect nucleotide, base editing was a great solution for it!
Similar to CRISPR, Prime editing uses the same components: Cas-9 protein, pegRNA (which has the same function as gRNA, it guides Cas-9.) Additionally, there is a component called the reverse transcriptase enzyme.
So, let’s break down how Prime Editing works:
Step1: Cas-9 only cuts one strand of a double helix.
Step2: A new type of RNA called pegRNA targets the location of DNA.
Step3: Another protein attach to Cas-9, a reverse transcriptase enzyme creates a new DNA strand from RNA and inserts it to the right spot, creating complementary bases so that they would repair themselves.
Now, you might be wondering what exactly the big differences between CRISPR and Prime Editing are. There are two important differences:
- Scientists designed the Cas-9 in a special way so that only one strand of DNA would be cut and is edited on a single open side.
- A new protein called Reverse transcriptase enzyme finds the base pairs and does the work of making a new DNA strand from RNA and paste it at the right spot.
As you can see, what’s really interesting is that Prime Editing doesn’t cut two strands of a double helix like CRISPR does. This eliminates the possibility of cutting the normal segments of DNA unintentionally, which is the biggest downside of CRISPR.
Yay, problem solved!
What’s also really fascinating is that Prime Editing can cure almost 90% of genetic errors. 90%!! Liu and his team have already tested these in more than 175 different edits including human and mouse cells. In the near future, Prime Editing may be a trusted medical treatment and would be able to help many patients with fewer byproducts, more precision and flexibility of curing different kinds of diseases.
Prime Editing is the next generation of our medical treatment.
Personally, I’m very excited to see how Prime Editing would change the medical field in the future. Diseases such as sickle cells, Tay-Sarchs, and HIV infections in human embryos have already been cured by Prime Editing. I’m looking forward to see what other diseases could be cured by Prime Editing.
So, what’s next?
It may work in human cells now, but having it perform well in different kinds of cell in other living bodies would be another challenge. Currently, Dr. Liu is examining Prime Editing in order to be globally accepted as a new medical treatment.
Some engineers predict that Prime Editing will help create more cells to recover patients’ diseases and to have access to Alzheimer’s cells instead of having a look at it after death. In addition, they predict that it may help computer algorithms for self-diagnosis which will have a huge impact on future autonomous systems.
Although this is seen as a superior gene editing solution and an important discovery for both the medical and the bio-molecular field, I believe that it may have a few ethical issues for the society to consider. Gene editing technologies are expensive and it may only be accessible to the wealthy. Also, like for designer babies, genetic alternations may change our next generation for both good and bad. What if people use this technology to purposely experiment with putting diseases into human bodies…?
As this technique is relatively new, I’m not sure that these developments would take place anytime soon but that is why we have to pay close attention to Prime Editing.
I am very excited to see how these new scientific discoveries and innovations could change our lives!
MY CONCLUSIONS…
Here are the key takeaways of Prime Editing.
- Prime Editing is a super upgraded version of CRISPR.
- Unlike CRISPR, Prime Editing only cuts one strand of a double helix, which decreases the risk of damage to the normal segments of DNA. Prime Editing uses a new protein called the Reverse transcriptase enzyme.
- Currently, Dr. Liu (the inventor) is going through many tests in order for Prime Editing to be globally accepted. If accepted, Prime Editing will help to support and expand many scientific discoveries and innovations in the future.
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Thanks for reading! Feel free to share your thoughts on this topic! :)
