Staying in Tune with Prime Editing

I play guitar every single day. Because of my daily practice, I find that my high E string always unravels and becomes loose. There are two solutions to the out-of-tune string. First, I can re-string or replace the string. It’s an easy thing for me to do, but it can get tedious when I do it every single time the string gets out of tune. The other solution is for me to tune the string with the tuning peg, twisting and turning the peg with precision until the right note is strummed. I find that tuning is the better solution; the precision I have while tuning the string results in the perfect sound.

Gene Editing

Imagine a world where genetic disease/defects are no longer a problem. You no longer have to worry about being a carrier of a disease and passing it down to your children. And even if you or someone you love ends up inheriting a genetic disease, there are safe cures & treatments that have been tested.

This is all possible now with Gene editing. Gene editing is where DNA is modified, inserted, or deleted in an organism’s genome. It can cure many genetic diseases that were once deemed “incurable.”

via sciencemag.org

Diseases like cystic fibrosis and sickle cell anemia are now curable, making gene editing a vital breakthrough.

“Over 1/5th of the human population has some form of a genetic disorder.”-Annals of Internal Medicine, 2017

In 2015, gene editing was able to save the life of a year-old girl, who suffered from “untreatable” leukemia. Doctors “removed immune cells, editing them so they’d go after cancer cells while also resisting a chemotherapy drug, and then injecting them back into her,” says an article by The Atlantic. But gene editing is not limited just to correcting genetic mutations. It can also be used for:

1. Crops, to grow a bigger yield and make them more sustainable
2. Designer Babies

There are three types of gene editing (currently):

1. CRISPR
2. Prime Editing
3. Base Editing Technologies

What is CRISPR?

How CRISPR Works, from Cambridge.org

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a technology used to edit genes, either by changing or cutting out the gene entirely. First discovered in bacteria, CRISPR was used to protect the bacteria from things like viruses. CRISPR occurs in 4 steps:

1. The Cas9 enzyme uses a guide RNA to lead it to the desired part of the DNA.
2. Once the guide RNA binds with the DNA, the Cas9 cuts both strands of the desired part of the DNA target.
3. Once the specific gene is cut, CRISPR relies on the cell’s repair system to fix the damage done by Cas9, making the necessary edits.
4. Voila! The gene is edited and the mutation is fixed

So, What’s the Problem?

While it may seem like the ideal method of gene editing, just like how I replace the string on my guitar every time it gets loose, CRISPR also comes with a few problems of its own.

The cell’s repair system is quite unreliable, paving the way for “off-target” effects and other kinds of weaknesses.

“The cell will try to switch things back together, but it doesn’t really know what bits of DNA lie adjacent to each other” -Allan Bradley, a geneticist from the Wellcome Sanger Institute in Hixton, UK.

The repair system can lead to an uncontrollable amount of changes, varying between cells. Although scientists can guide the edits made in a genome, the DNA’s repair system is likely to make small modifications (deletion or insertion), making it incredibly difficult to read and interpret. Researchers have even said CRISPR is not the most precise method of gene editing.

“It’s proven difficult to use these molecular scissors to make precise DNA changes in most cell types.” -David Liu, a biologist at Harvard, MIT and the Broad Institute in Cambridge, Mass

Alright, Then What Can I Do? Prime Editing

Now comes in prime editing: the new, precise, and overall better method of gene editing. Prime editing is like tuning the loose string on my guitar perfectly — simple, easy, effective.

Prime editing is very similar to CRISPR, but there are a few key differences that make it stand out.

Venn Diagram of Prime Editing and CRISPR, made by me.

Here are the steps of Prime Editing:

via the-scientist.com

1. The Cas9 enzyme uses RNA as a guide to the desired part of the DNA.
2. The enzyme snips only one strand of the DNA target.
3. Primer, a part of the guide RNA, binds to the desired gene.
4. The new DNA sequence is now placed in the gene by the guide RNA.
5. 5. There might be a mismatch, but it can be easily detected by the cell’s repair system and is then simply corrected.

So, why is this important? Well, this method significantly reduces the chance of “off-targets” occurring in the DNA!

The Potential of Prime Editing

Prime editing does not rely on the ability of the cell’s repair system to divide(In CRISPR, the cells divide to fix the damage). What does this mean? It can fix genetic mutations in places where cell division is low, like the nervous system. Genetic diseases like Huntington’s Disease, Parkinson’s Disease, and Alzheimer’s can now potentially be treated through gene editing.

Crops

via fortune.com

Prime editing can be used to improve the lifespan and quality of crops. By using gene editing to create a bigger yield, there is now potential for more food that is healthier and more nutritious. It is currently being used on commercial crops like wheat, rice, and corn.

Genetic Disease

David Liu says his team has already used the new approach to perform more than 175 edits in human cells in laboratory dishes, including fixing genetic mutations that cause sickle cell disease and Tay-Sachs disease. Doctors are already trying to use CRISPR to treat sickle cell patients. Prime editing can potentially be used to treat over 7,000 “untreatable” disease.

Conclusion

While a loose high E-string may lead to some poor music, the wrong genome can be life-changing and sometimes life-threatening to individuals. Yes, the stakes are higher, making tuning the gene perfectly even more pivotal. CRISPR, while having undeniable benefits, still comes with uncertain risks that may be too high to ignore. Luckily, Prime Editing comes with all the benefits of CRISPR but less of the risk. A world where genetic diseases are curable is at our fingertips. Now that’s music to my ears!