Representation of Genetic Modification. (Image via abc.net.edu)

A Prime Time For Gene Editing. Beginner’s Guide: Prime Editing 101.

What if it were possible to edit genetic code, and remove a person’s risk for specific chronic diseases? Such a personalized appeal, to vulnerable patients, would alter all of healthcare and is at the core of precision medical goals. Thanks to the researchers at the Broad Institute of MIT and Harvard, clinical laboratory diagnostics based on precise gene-editing techniques may be closer than ever! Researchers were able to develop a new CRISPR genome editor by integrating two of the most critical proteins, CRISPR-Cas9, and a reverse transcriptase into a single machine method. In due time, this new and advanced genome editor will undoubtedly become a major development trend and influence the Medical Industry considerably, in the future!

Genetic Engineering and Gene Manipulation Concept. (Image via rafer.es)

In this article, I will discuss:

  1. What is Prime Editing?
  2. How did Scientists discover Prime Editing?
  3. How does it Work?
  4. Why is it important?
  5. How is it different from CRISPR?
  6. What might the future hold for Prime Editing?

What is Prime Editing?

In a paper published by Nature, the authors claim that Prime Editing has the potential to correct up to 89% of disease-causing genetic variations. Developed by researchers at the Broad Institute of MIT and Harvard, it is described as a versatile and precise genome editing method that is more powerful, accurate, and flexible than CRISPR. It is a technology utilized by scientists to re-edit the genetic code to change mutations and eliminate sequence errors which cause debilitating diseases like Cystic Fibrosis, Sickle Cell Anemia, Phenylketonuria, etc.

A Few of the Researchers at the Broad Institute of MIT and Harvard. (Image via. ec.europa.eu)

How was it Discovered?

For scientists to understand and discover Prime Editing, they first had to grasp a strong understanding of CRISPR Cas9, and the role of the protein. After some research, scientists were able to conclude that the natural role of CRISPR Cas9, lies within the cell’s bacterium. They also concluded that this protein plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications.

A Basic Diagram, which shows the processes, that the protein CRISPR Cas9 undergoes during genetic engineering. (Image via Longevity.org)

According to Xtalks, CRISPR is a way for the bacterium to remember what viruses it has been infected by in the past. With these integrated pieces of viral DNA, the bacterium creates a replicate RNA of it, which bonds to the protein Cas9. The main function, of Cas9, is to cut sections of DNA, and with the replicated RNA, it surveys through all the DNA of the bacterium, until it finds a perfect match. Once the match is discovered, the Cas9 jumps into action and cuts both strands of DNA that have entered the bacterium, thereby eliminating the threat. According to Michael Lim, a visionary in the healthcare field, one can think of the Cas9 complex, as a bodyguard doing surveillance for intruders.

A Virus injecting its Viral DNA, into a Host Cell. (Image via Xconomy.org)

Upon realizing, the genomic editing ability of the Cas9 protein, scientists began to utilize unmodified and altered versions of Cas9, in conjunction with a guide RNA, and eventually a reverse transcriptase, an enzyme used to generate complementary DNA, from an RNA template. The use of a guide RNA and a reverse transcriptase ultimately led to the development of Prime Editing.

How does it Work?

According to the Broad Institute, scientists were able to engineer and modify the Cas9 protein, in such a way, so the protein only cuts one strand of DNA, instead of two. Through the use of a modified Cas9 enzyme, known as Cas9 nickase, scientists were able to develop a new gene-editing technique, which makes only Single-Stranded DNA cuts. This method allows researchers to edit more types of genetic mutations. Below, is a Genome-Editing diagram that explains more, about the entire process. One analogy that we all can use when describing Genome Editing, is thinking of it as a search and replace function in Microsoft Word.

A diagram depicting the steps of search and replace genome editing. (Diagram from the Broad Institute)

Why is Prime Editing Important?

When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development and can cause a severe medical condition. A condition caused by mutations in one or more genes is called a genetic disorder. Though, what makes it much worse, is the fact that most genetic disorders are hereditary, meaning the offspring of anyone with a genetic abnormality, have a higher chance of inheriting that disease.

Cystic Fibrosis is a Hereditary Disease. In the general population, about 1 in every 100,000 newborns has Cystic Fibrosis. (Image via Spectrum Health)

A study in 2017 published in the Annals of Internal Medicine, stated that the Fraction of people with Genetic Disorders is close to 20 percent. This means, that if a cure for genetic disorders is not found, the percentage of the population that has a hereditary disease will grow aggressively. Finding a cure will prevent a rise in this percentage, and will also improve the quality of life for so many!

While a few disorders have been treated through gene therapy, the only way to cure the majority of genetic disorders is through the reprogramming of mutated DNA. Through the technology of Prime Editing, we can significantly expand the capabilities of genome editing and can help decrease the impact of genetic diseases in our society.

After researching more about the impacts that genetic diseases have on a family, it makes me very grateful, that I was lucky enough to be born, as a healthy and strong child.

Click Here, to read a touching article, about a family’s experiences, when their child was diagnosed with a rare genetic disease, called ataxia-telangiectasia.

A-T is a rare, neurodegenerative disease that affects children, giving them combined symptoms of cystic fibrosis, muscular dystrophy, cerebral palsy, and even cancer. (Image via Global Genes.org)

Even though Gene-Editing has the ability to cure the majority of genetic disorders, through the reprogramming of mutated DNA, it also has the ability to create something completely new and absolutely shocking! This is what most like to call, “Designer Babies”. As asserted by Wikipedia, a designer baby is a baby whose genetic makeup has been selected or altered, often to include a particular gene or to remove genes associated with the disease.

With the use of CRISPR technology, scientists could make designer babies, who are immune to certain viruses and can be associated with certain skills. (Image via. NextBigFuture.com)

In 2015, Chinese researchers first edited the genes of a human embryo in a lab dish. Through the use of a powerful gene-editing tool, CRISPR, they were able to make the birth of humans genetically modified in vitro fertilization, a general possibility.

Through Prime Editing, scientists and researchers claim, that it is possible to make the Designer Baby have no inherited diseases, and a low risk of various diseases and viruses, such as Breast Cancer, and Alzheimer’s. Apparently, it is also possible, to mutate the child’s DNA in such a way, as to give the child perfect vision, a High IQ, and even various athletic skills.

After hearing all of that it sort of makes me wish I was born a few decades later, and become a Designer Baby, myself!

A short process, that scientists are considering to use, through genetic screening, to create a designer baby! (Image via. UBC Wiki)

How is Prime Editing different from CRISPR?

As mentioned above, CRISPR technology is a simple, yet powerful tool for editing genomes. This technology allows researchers to easily alter DNA sequences and modify gene function. According to Live Science, CRISPR Cas9 is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA.

CRISPR Technology cutting through various strands of DNA. (Image via Science News.org)

Although indistinguishable at first glance, CRISPR and Prime Editing have many principal differences.

  • Prime Editing uses a modified form of the Cas9 enzyme, which is designed to only cut one strand of DNA at a time, in comparison to the unmodified form of Cas9 used in CRISPR which cuts both strands of DNA.
  • Prime Editing uses a modified form of RNA, which is substantially larger than standard RNAs used for CRISPR gene editing.
  • In addition, during the process of Prime Editing, there is a reverse transcriptase bonded to the Cas9 enzyme which is used to generate complementary DNA, from an RNA template.
  • According to David Liu, the Vice-Chair of the Faculty at the Broad Institute of Harvard and MIT. The Broad Institue conducted a study, of a side-by-side comparison of off-target editing between a Cas9 nuclease, and prime editing at known Cas9 off-target sites, with the result that prime editing is far less prone to off-target editing.
  • Yet, one of the biggest differences between these technologies is the extent of the research that has been conducted on Prime Editing. CRISPR has been around for about 7–8 years and is much more heavily researched, as Prime Editing was only published in October 2019.

CRISPR is a more heavily tested technology, that uses an unmodified form of Cas9, cuts through both strands of DNA, and has more off-target effects.

Prime Editing is a newer, more accurate, and precise technology, uses a modified form of Cas9, with a reverse transcriptase attached. In addition, it only cuts through one strand of DNA at a time and has less off-target effects.

I strongly suggest that anyone interested should watch this captivating and compelling video that explains, How Genetic Engineering will Impact our World!

Precise CRISPR tool enhanced by Enzyme-Engineering. Uses a more advanced method called Base Editing. (Image via. Science Circle)

What Might the Future Hold for Prime Editing?

Prime Editing presents a new way to make changes to DNA while avoiding some of the drawbacks of traditional CRISPR. Prime Editing has principal differences from CRISPR, which give it massive potential in the future, as it is more advanced, precise, and detailed than any other genome editing software. Prime Editing is currently being used for commercial use on important crops, like corn, wheat, and rice.

Prime Editing Being Optimized for Important Crops. (Image via TvNews.com)

This demonstrates the versatility and prospective that Prime Editing has had in a multitude of fields. When addressing the potential, that Prime Editing has in genetics, it can impact the lives of millions of people and can help decrease the impact of genetic diseases in our society.

Though, according to Synthego, Genetic Modification can run into its fair share of future problems, particularly in ethics.

Ethics of Gene Editing. (Image via. Harvard Gazette)

Ethics will always play a role in new, experimental technologies. According to the National Human Genome Research Institute, Safety is the primary concern. Researchers and Ethicists who have written and spoken about Genome Editing, generally agree that until genome editing is deemed safe through extensive research, it should not be in use for clinical purposes. This is due to the off-target genome changes, and the inability to determine the long-term effects of the use of this technology triggers a lot of fear and suspicion.

In addition, as with many new technologies, there is a heavy concern that genome editing will only be accessible to the wealthy and will increase existing disparities in access to health care and other interventions. This also brings up the question, How impoverished families would be able to afford or even undergo the treatment of genetic modification?

Genome Editing can increase the disparities between the Rich and the Poor. (Image via Genetic Literacy Project)

Lastly, some people also worry that it is impossible to obtain informed consent for specific therapy, as the patients affected by the edits are in fact, the family’s future generations. Researchers and Biophysicists also worry about the possibility of obtaining truly informed consent from prospective parents, as long as the risks of germline therapy are unknown.

The effects of Hereditary Diseases can impact the family’s future generations, in somewhat of a random sequence. (Image via. Genetics Home Reference. (GHR))

In my personal opinion, in terms of designer babies, the use of genome editing for clinical purposes, and even from an ethical standpoint; I believe that while there are some risks attached to genome editing, with proper testing it can completely change the world that we currently live in. From almost superhuman babies, to saving the lives of thousands by curing the majority of genetic disorders, genome editing has the ability to directly impact our Medical, and even the Agricultural industry considerably, in the future!

Key Takeaways:

  • Prime Editing is a technology utilized by scientists to re-edit the genetic code to change mutations and eliminate sequence errors that cause debilitating diseases.
  • Through the technology of Prime Editing, we can significantly expand the capabilities of genome editing and can help decrease the impact of genetic diseases in our society.
  • Although indistinguishable at first glance, CRISPR and Prime Editing have many principal differences, where Prime Editing offers more opportunities and is more detailed and precise.
  • The future of Prime Editing is very bright, yet more testing and research must be conducted, in order for this technology to be published, and be in a position, to impact our society.

Hopefully, you enjoyed reading my article. I hope you learned something new and gained a better understanding of Prime Editing as a whole!

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