Project Prime Editing: Loading Genetic Blueprint 101…

Dear 8-year-old Carlos,

When I was 8 years old, I looked up into the night sky, closed my eyes, and imagined the power of where whatever is not satisfying can be altered to your desires and forever have the perfect version of yourself… Oh, wait. Fortunately or unfortunately, it is possible to rewrite scripts of humanity, from nature to civilization to an individual’s genes.

Before I discovered the universe of gene editing, I was living fantasy whether I could change details that were forever to remain in place. With my personal expedition of gene editing and rewriting your own DNA, everything is possible.

What is DNA to begin with? DNA (Deoxyribonucleic acid) is broken down into four individual nitrogenous bases: cytosine, guanine, adenine, and thymine. These individual bases define the foundation of our genes and make up our genetics that makes up every aspect of our traits. Without these strands of genetic coding, we would cease to exist, and any slight margin of alteration or error in our genetic codes could lead to catastrophe. Unfortunately, there are certain situations where fate takes a turn for the worse. Is there a solution to a problem where genetics was given and can’t be replaced?

The answer is both a yes and a no. However, if just one modification of a single gene in your body occurs, the result is going to be fatal. Through the studies of the World Health Organization, this occurrence is classified as a “monogenic disease”. Monogenic diseases originate from an adjustment of a single gene that can lead to interference and modification of all the cells in the human body. Unfortunately, there is more than one form other than monogenic diseases. The foundation of a genetic disorder must derive from alteration or change to a single gene code inside a living organism. The treatment towards the disorders attacks the small details, but never truly heals the core or the foundation of the problem, which in this case is the mutation in the DNA. Science and technology have breathed answers and solutions to obstacles that were mountains into hills.

Enter: PRIME EDITING.

WHAT IS PRIME EDITING?

Imagine prime editing as Grammarly: it has the ability to correct our mistakes while typing. Prime Editing gives us the power to rectify mutated strands of DNA that cause diseases such as cystic fibrosis, sickle-cell anemia, or Tay-Sachs disease. Grammarly will suggest more formal or complex vocabulary to replace the original context. With Prime Editing, we go into the atomic level to locate a mutated gene, delete the original gene, and replace the gene with genetic transformations through the desire of the individual going through the process. An example of a genetic disorder and its causes is cystic fibrosis.

Cystic fibrosis (CF), this genetic disorder disturbs the usage of mucus in your body. Mucus is necessary for your organs and your internal systems such as your digestive system. However, CF alters the mucus to become super thick and into a tacky-glue paste. The mucus will impede passageways throughout your body such as tubes or ducts. As time takes its toll, the mucus will reach and build up inside of your lungs, making it demanding for you to breathe properly. The mucus can potentially trap germs and infections that will lead to an even bigger obstacle like cysts (fluid-filled sacs) and/or fibrosis (damage to tissues; scars). Hence the name cystic fibrosis.

So why is it essential to introduce gene editing to society?

Genetic disorders have targeted so much more of the global population that what was initially perceived by scientists. Scientists initially believed that genetic disorders affected around 7% of the global population. Unfortunately, a research paper published in 2018 by the National Human Genome Research Institute raises the percentage to a shocking 19%. That is millions of people worldwide affected by a genetic disorder.

Nearly all genetic disorders are hereditary, meaning they are derived from your parents with genetic flaws, which will raise the chances of the offspring to acquire the genetic disorder. Without a cure or a solution to the uprise of genetic disorders, the population with genetic abnormality will gradually increase to a point where there is no solution. With an “antidote” to the dilemma of genetic disorders, we can gradually lower the percentage of the global population with genetic disorders and also increase the lifespan and overall health of the individuals who have a genetic disorder the opportunity to live life to its potential.

Currently, the only formula for hereditary diseases is “rebooting” the living organisms’ mutated DNA through Prime Editing. Through the lenses of enhancements in technology, the possibility to create humans from scratch is slowly becoming a reality. Someday children will dream of becoming their favorite Marvel hero and find out it is completely possible! I wish one day I could have the power of teleportation.

But how does this mind-blowing discovery performs its magic of editing DNA?

Below here is a diagram that simplifies the conversion of altering the genes in mutated DNA.

I believe that this informative diagram is processable for everybody to potentially have a discussion with an expert in the field of genome editing. However, some people may be asking:

What in the world are CRISPR AND CAS-9?

CRISPR-Cas-9, better known as CRISPR, is where the beauty of gene editing originated from Prime Editing. Using Cas-9 enzymes, scientists are able to extract strands of DNA to make precise edits and results to fully desired and altered DNA.

Below is a link to an informative video that clarifies CRISPR- and Cas-9.

What makes Prime Editing and CRISPR unique from one another?

After reviewing the purpose of CRISPR, you may be questioning yourself if Prime Editing or CRISPR is more reliable than the other. At first glance, yes, these two genome editing systems are compatible with each other. However, they are more separate than what you initially believed. Below is a Venn Diagram explaining the similarities and differences between these two enhancements in genome technology.

Prime Editing is an enhanced version of the original genome editor, CRISPR. Prime Editing uses an altered form of the CAS-9 enzyme, CAS 9 Nickase, which is performed to only cut through a single strand of DNA at a time, whereas in CRISPR, it is modified to cut through both strands of DNA at the same time, which could lead to greater problems such as inadequate cuts through the DNA and possibly form new mutations. With the progress in technology, Prime Editing has been able to simplify genetic editing by isolating DNA is singular strands of RNA (Ribonucleic acid), which contains more precise genetic coding in a single strand for more accurate change for the requested DNA. This additional buffer to editing provides Prime Editing with precision and accuracy that unfortunately CRISPR does not contribute to the process. A study was done by the Broad Institute in October of 2019 tested the accuracy of the genome-editing machinery. They set 4 genetic mutations across the board for Prime Editing and CRISPR-9 to “search and replace”. What was surprising about the results was CRISPR-9 detected 16 individual locations to replace, while Prime Editing edited only 3 out of the 4 loci (loci is the position of the chromosome in the strands of DNA). Despite the research, CRISPR-9 existed since 2011, while Prime Editing has been around since early November of 2019, so more results and discoveries have been observed through CRISPR-9 than the improved Prime Editing, which may be less reliable due to inadequate research and tests.

Through science and results, this is a breakthrough for Prime Editing in this period of civilization. However, Prime Editing has expanded its boundaries by not just editing human genetics but also manufacturing and altering whole-wheat products and grains (rice, bread, corn, etc.). Prime editing is approaching its first peaks in the research of genome-editing and manufacturing food products. This would affect society as a blessing and a burden.

What lies ahead for the fate of Prime Editing?

The privilege for humanity to have access to genomics is going to be a cure for the hundreds of millions of people with a genetic disorder to have a second opportunity in life and eventually set greater standards and expectations for uprising technology.

The concern of introducing Prime Editing to available use to everybody is the safety of every individual, let alone any malfunction or marginal error of the technology will seal the fate of the long-term usage of Prime Editing. Is this a risk we can moderate or potentially resolve for the security of the population and ensuring forever use of Prime Editing? Next, Prime Editing can also modify a human embryo and the upcoming generations to come. So obviously, consent/permission will be required before taking the risk and opportunity for enhancements in genomics to the embryo. Finally, Prime Editing is revolutionary, but undergoing this treatment comes at a hefty cost. One day technology will grant us the privilege for families in poverty to undergo the exact treatments of genetic editing without paying full price. Maybe in the future, we can resolve the inequality of ethics around the globe to surpass the bumps and mountains Prime Editing will have to encounter to leave its stepping stone in the world of technology.

When I was 8 years old, I stared deeply into the cosmos, freed my mind of distractions, and visioned the ability to rewrite personal deficiencies into a view I was proud of… We could rewrite the scripts of humanity with our own coding…our own genetics…A REBIRTH OF IMMORTALS…

Sincerely,

15-year-old Carlos

Most Valuable Points (MVP’s):

• Prime Editing- simplified, a “search and replace” machinery with the capacity to literally alter living organisms’ genomes.
• With the unfortunate uprise of genetic disorders, Prime Editing is a potential treatment to decrease the number of hereditary diseases. and give individuals a second opportunity.
• Although Prime Editing and CRISPR-CAS9 have similarities and identical origins, Prime Editing is much more accurate and provides greater setpoints and advantages to genome editing than CRISPR-CAS9.
• One day in the upcoming years we will adjust the inadequacies Prime Editing faces in the present day to make genome editing the reality of tomorrow.