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PAC-MAN: From Video Games to COVID-19 Treatment

By Cayla Solomon

My name is Cayla Solomon. I am a junior at Pacific Ridge High School just north of San Diego. My goal through this blog is to share stories about new advances and discoveries that scientists are making related to my interest in genetics.

What if we had the ability to treat blindness, prevent Alzheimer’s, or even cure cancer? I remember sitting in my ninth grade biology classroom watching the movie Gattaca. It revolved around the idea of genetic modification– altering the genetic code to prevent diseases, enhance attractiveness or even intellectual abilities (fun fact, the word “Gattaca” is made up of all the letters that represent the four nucleotide bases of DNA!). Back in 1987, just thirty years ago, when this movie was released, the idea of genetic engineering seemed complete science fiction. Even as I watched this movie a few years ago, it was hard to wrap my mind around the fact that it could be possible to prevent genetic diseases or cure some of the most deadly illnesses and viruses. But what if I told you that these feats are possible today with the development of CRISPR technology? CRISPR is a gene editing system that allows scientists to identify and eliminate sequences of DNA in the human genome. If you are like me, you are most likely sitting at home, watching the news, hoping that it will soon be safe to see your friends without wearing a mask and wondering if we will ever have a treatment for coronavirus. If we can treat diseases and viruses through the use of CRISPR, is it possible to treat coronavirus too? This is the exact same question I had and is what prompted my research to see if any current efforts are being made to treat COVID-19 through genetic engineering and, to my surprise, there are!

For months on end, the world has been focused on taking control of COVID-19– the cause of one of the worst global pandemics in history, with a mortality rate ten times higher than that of the yearly seasonal flu. As most of the world is focused on a preventative approach such as a traditional vaccine against the virus, some scientists are experimenting with alternative treatments involving the use of CRISPR technology. One such group is a team of bioengineers at Stanford University who are using an approach called PAC-MAN, or prophylactic antiviral CRISPR in human cells. Coronaviruses enter our cells and hijack the machinery in order to release and replicate their own RNA genome. This prevents the normal function of the original cell. If our immune system does not recognize this foreign invader or attack it, the newly replicated viruses can leave the host cell and infect other cells, spreading rapidly throughout the body. PAC-MAN technology is used as a way to treat the virus once someone is infected with it by blocking the virus’ ability to reproduce, thus eliminating it from the body. Just as the Pac-Man from the video game catches or consumes little dots, this system works similarly by targeting and “cutting out” specific spots within the genome of the virus that code for its ability to enter human cells and replicate itself. The PAC-MAN/CRISPR system works by using a “guide RNA” that helps navigate an enzyme called Cas-13 to the spot in the coronavirus genome that codes for its ability to reproduce. The Cas-13 enzyme cuts the genome at this spot, which completely neutralizes the virus.  

However, the Stanford team working on PAC-MAN ran into a problem: how can PAC-MAN be effectively delivered to the lungs where COVID-19 does the most damage? Once PAC-MAN entered the body, scientists had no way to direct it to the desired target. They addressed this by reaching out to the Berkeley Lab’s Molecular Foundry where they had been working on synthetic peptides, short strings of amino acids with lipids (called lipitoids) that have the ability to deliver DNA and RNA into cells. The Molecular Foundry is a nanoscience research center that is funded by the U.S. Department of Energy, and assists users from around the world with cutting-edge expertise. Just as a GPS directs you to your destination, lipitoids work in this same manner. The Stanford scientists used these lipitoids in combination with PAC-MAN to deliver the technology to the desired region of the body, in this case the lung cells. They tested this lipitoid/PAC-MAN system in a solution in a petri dish containing fragments of the virus and found that it successfully reduced the amount of SARS-CoV-2 in the solution by more than 90%. While this is one method of directing the CRISPR/PAC-MAN technology, there are other methods being explored. One of these is a nebulizer, which is a mist-inhaling device that allows the treatment to be inhaled and directly delivered to the lungs. Moving forward, the Stanford team is planning on testing this technology in animal trials. As testing continues, this could very well be the foundation upon which a treatment for COVID-19 is built.

The development of CRISPR–despite some elements of it being ethically debatable (a subject for a future blog!)–has the potential to not only greatly impact the scientific community, but also transform our lives and direct our future. I believe that, if used for the purposes of treating viruses or genetic diseases, such as cancer, cystic fibrosis, or sickle cell anemia, CRISPR can be a powerful tool used for global health benefits. In addition to COVID-19, it could potentially be used to target other viral strains, including the yearly seasonal flu. And who knows, maybe in the near future, PAC-MAN will no longer be recognized as simply a video game. 

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